The insect fat body is comparable to the liver and adipose tissue in vertebrates,and plays a pivotal role in energy metabolism,nutrient storage,and reproduction.During metamorphosis,the fat body is disassembled via pr...The insect fat body is comparable to the liver and adipose tissue in vertebrates,and plays a pivotal role in energy metabolism,nutrient storage,and reproduction.During metamorphosis,the fat body is disassembled via programmed cell death and cell dissociation.After adult eclosion,the fat body is reconstructed either by repopulation from the remaining juvenile fat body cells or by differentiation from adult progenitor cells.This reconstruction is a prerequisite for initiating the extensive synthesis of vitellogenin(Vg),which is necessary for the maturation of eggs.Despite its significance,the underlying mechanisms of this reconstruction remain inadequately understood.Transcriptome analysis of the fat bodies from migratory locusts at 0-5 days post adult emergence revealed 79 genes associated with chromatin remodeling.Weighted gene co-expression network analysis indicated a positive correlation between chromatin remodeling and fat body reconstitution.Protein-protein interaction analysis revealed that brahma,which encodes the catalytic subunit of the SWI/SNF chromatin remodeling complex,is crucial for post-adult-eclosion fat body development.qRT-PCR analysis demonstrated that the levels of brahma mRNA in the fat body are progressively increased during the previtellogenic stage,then reach the peak and remain elevated in the vitellogenic phase.Furthermore,brahma is expressed in response to gonadotropic juvenile hormone(JH).Knockdown of brahma led to a marked reduction in Vg expression within the fat body,along with arrested ovarian growth.These findings shed light on the involvement of brahmamediated chromatin remodeling in JH-stimulated fat body reconstruction and reproduction of adult female locusts.展开更多
Objective:To investigate the regulatory effects of acupuncture and moxibustion on chromatin remodeling complex core catalytic subunit of Brahma-related gene 1(Brg1),histone deacetylase(HDAC)3,HDAC9,and males absent on...Objective:To investigate the regulatory effects of acupuncture and moxibustion on chromatin remodeling complex core catalytic subunit of Brahma-related gene 1(Brg1),histone deacetylase(HDAC)3,HDAC9,and males absent on the first(MOF)in the colon tissue of rats with Crohn disease(CD).Methods:Using the random number table method,60 male Sprague-Dawley rats were divided into 5 groups,including a normal group,a model group,an acupuncture group,a medicinal cake-insulated moxibustion group,and an acupuncture-moxibustion group,with 12 rats in each group.CD rat models were prepared using 2,4,6-trinitrobenzene sulfonic acid(TNBS)in all groups except the normal group.The normal and model groups received no interventions.In the acupuncture group,rats were intervened with acupuncture at bilateral Zusanli(ST36)and Shangjuxu(ST37),20 min/session,once a day.The medicinal cake-insulated moxibustion group received medicinal cake-insulated moxibustion at Qihai(CV6)and bilateral Tianshu(ST25)with 2 cones per point per session,once a day.The acupuncture-moxibustion group received both acupuncture and moxibustion interventions simultaneously.Each intervention was performed for 10 consecutive days.Observations included general condition,disease activity,macroscopic damage,and pathological changes in the rat’s colon tissue.Realtime fluorescence quantitative polymerase chain reaction was used to measure the mRNA expression of chromatin remodeling-related enzymes Brg1,HDAC3,and HDAC9,while Western blotting detected the protein expression of Brg1,HDAC3,HDAC9,and MOF in rat’s colon tissue.Results:The model group showed significantly increased diarrhea score,occult blood score,macroscopic damage score of colon tissue,and colon macroscopic damage index(CMDI)score,as well as elevated mRNA expression levels of HDAC3 and HDAC9,protein expression levels of HDAC3,HDAC9,and MOF,and decreased mRNA and protein expression levels of Brg1 compared to the normal group(P<0.01).In contrast,compared to the model group,the diarrhea score,occult blood score,macroscopic damage score,CMDI score,mRNA expression levels of HDAC3 and HDAC9,and protein expression levels of HDAC3,HDAC9,and MOF were significantly reduced(P<0.05 or P<0.01),while the mRNA and protein expression levels of Brg1 were significantly increased(P<0.01)in the acupuncture group,the medicinal cake-insulated moxibustion group,and the acupuncture-moxibustion group.Conclusion:Both medicinal cake-insulated moxibustion and acupuncture,either used alone or in combination,can regulate the abnormal expression of chromatin remodeling-related enzymes Brg1,HDAC3,HDAC9,and MOF in the colon tissue,thus reducing colon inflammation in CD rats.展开更多
Tissue stem cells(TSCs),which reside in specialized tissues,constitute the major cell sources for tissue homeosta-sis and regeneration,and the contribution of transcriptional or epigenetic regulation of distinct biolo...Tissue stem cells(TSCs),which reside in specialized tissues,constitute the major cell sources for tissue homeosta-sis and regeneration,and the contribution of transcriptional or epigenetic regulation of distinct biological pro-cesses in TSCs has been discussed in the past few decades.Meanwhile,ATP-dependent chromatin remodelers use the energy from ATP hydrolysis to remodel nucleosomes,thereby affecting chromatin dynamics and the regulation of gene expression programs in each cell type.However,the role of chromatin remodelers in tissue stem cell fate determination is less well understood.In this review,we systematically discuss recent advances in epigenetic control by chromatin remodelers of hematopoietic stem cells,intestinal epithelial stem cells,neural stem cells,and skin stem cells in their fate determination and highlight the importance of their essential role in tissue homeostasis,devel-opment,and regeneration.Moreover,the exploration of the molecular and cellular mechanisms of TSCs is crucial for advancing our understanding of tissue maintenance and for the discovery of novel therapeutic targets.展开更多
Environmental stress from climate change and agricultural activity threatens global plant biodiversity as well as crop yield and quality.As sessile organisms,plants must maintain the integrity of their genomes and adj...Environmental stress from climate change and agricultural activity threatens global plant biodiversity as well as crop yield and quality.As sessile organisms,plants must maintain the integrity of their genomes and adjust gene expression to adapt to various environmental changes.In eukaryotes,nucleosomes are the basic unit of chromatin around which genomic DNA is packaged by condensation.To enable dynamic access to packaged DNA,eukaryotes have evolved Snf2(sucrose nonfermenting 2)family proteins as chromatin remodeling factors(CHRs)that modulate the position of nucleosomes on chromatin.During plant stress responses,CHRs are recruited to specific genomic loci,where they regulate the distribution or composition of nucleosomes,which in turn alters the accessibility of these loci to general transcription or DNA damage repair machinery.Moreover,CHRs interplay with other epigenetic mechanisms,including DNA methylation,histone modifications,and deposition of histone variants.CHRs are also involved in RNA processing at the posttranscriptional level.In this review,we discuss major advances in our understanding of the mechanisms by which CHRs function during plants’response to environmental stress.展开更多
The Imitation Switch （ISWI） type adenosine triphosphate （ATP）-dependent chromatin remodeling factors are conserved proteins in eukaryotes, and some of them are known to form stable remodeling complexes with member...The Imitation Switch （ISWI） type adenosine triphosphate （ATP）-dependent chromatin remodeling factors are conserved proteins in eukaryotes, and some of them are known to form stable remodeling complexes with members from a family of proteins, termed DDT-domain proteins. Although it is well documented that ISWIs play important roles in different biological processes in many eukaryotic species, the molecular basis for protein interactions in ISWI complexes has not been fully addressed. Here, we report the identification of interaction domains for both ISWI and DDT-domain proteins. By analyzing CHROMATIN REMODELING11 （CH R11） and RINGLET1 （RLT1）, an Arabidopsis thaliana ISWI （AtlSWI） and AtDDT-domain protein, respectively, we show that the SLIDE domain of CHR11 and the DDT domain together with an adjacent sequence of RLT1 are responsible for their binding. The Arabidopsis genome contains at least 12 genes that encode DDT-domain proteins, which could be grouped into five subfamilies based on the sequence similarity. The SLIDE domain of AtlSWI is able to bind members from different AtDDT subfamilies. Moreover, a human ISWI protein SNF2H is capable of binding AtDDT-domain proteins through its SLIDE domain, suggesting that binding to DDT-domain proteins is a conserved biochemical function for the SLIDE domain of ISWIs in eukaryotes.展开更多
Plant reproduction requires the coordinated development of both male and female reproductive organs.Jasmonic acid(JA)plays an essential role in stamen filament elongation.However,the mechanism by which the JA biosynth...Plant reproduction requires the coordinated development of both male and female reproductive organs.Jasmonic acid(JA)plays an essential role in stamen filament elongation.However,the mechanism by which the JA biosynthesis genes are regulated to promote stamen elongation remains unclear.Here,we show that the chromatin remodeling complex Imitation of Switch(ISWI)promotes stamen filament elongation by regulating JA biosynthesis.We show that AT-Rich Interacting Domain 5(ARID5)interacts with CHR11,CHR17,and RLT1,several known subunits of ISWI.Mutations in ARID5 and RLTs caused a reduced seed set due to greatly shortened stamen filaments.RNA-seq analyses reveal that the expression of key genes responsible for JA biosynthesis is significantly down-regulated in the arid5 and rlt mutants.Consistently,the JA levels are drastically decreased in both arid5 and rlt mutants.Chromatin immunoprecipitationquantitative PCR analyses further show that ARID5 is recruited to the chromatin of JA biosynthesis genes.Importantly,exogenous JA treatments can fully rescue the defects of stamen filament elongation in both arid5 and rlt mutants,leading to the partial recovery of fertility.Our results provide a clue how JA biosynthesisis positively regulated by the chromatin remodeling complex ISWI,thereby promoting stamen filament elongation in Arabidopsis.展开更多
IL-6 plays important and pleiotropic roles in infection and inflammatory diseases,and its production needs to be tightly regulated.However,the epigenetic mechanism underlying Il6 gene transcription remains to be fully...IL-6 plays important and pleiotropic roles in infection and inflammatory diseases,and its production needs to be tightly regulated.However,the epigenetic mechanism underlying Il6 gene transcription remains to be fully elucidated.Here,we report that lysine-specific demethylase 2b(KDM2B),which demethylates H3K4me3 and H3K36me2,is required in macrophages and dendritic cells for the induction of IL-6 but not TNF-α,IL-1,and IFN-β.Compared to wild-type mice,KDM2B-deficient mice were more resistant to endotoxin shock and colitis,with a less severe inflammatory pathogenesis phenotype and decreased IL-6 production in sera.KDM2B selectively bound the Il6 promoter but did not alter histone demethylation;instead,KDM2B interacted with Brahma-related gene 1(Brg1),the core ATPase subunit of SWI/SNF chromatin remodeling complexes,to facilitate chromatin accessibility of the Il6 promoter.Furthermore,KDM2B directly recruited RNA Polymerase II to further initiate and promote Il6 transcription.Thus,our finding identifies a novel nonclassical function of KDM2B in gene-specific transcription initiation and enhancement of Il6 independent of its demethylase activity and adds new insight into the specific epigenetic modification mechanism of inflammatory immune responses.展开更多
Heterochromatin is characteristically more compact than chromatin is mediated by special histone modifications, euchromatin in the eukaryotic genome. The establishment of hetero- recruitment and propagation of heteroc...Heterochromatin is characteristically more compact than chromatin is mediated by special histone modifications, euchromatin in the eukaryotic genome. The establishment of hetero- recruitment and propagation of heterochromatin specific proteins, as well as formation of special primary and high order structures of chromatin. Chromatin remodeling factors are ATPases that can alter the conformation and/or positioning of nucleosomes along DNA in an ATP-dependent manner. There is increasing evidence implicating chromatin remodeling activities in heterochromatin in various organisms ranging from yeasts to humans. Chromatin remodeling factors play roles in the establishment, maintenance and epigenetic inheritance of heterochromatin, but the underlying molecular mechanisms have just begun to be investigated.展开更多
Gene transcription and new protein synthesis regulated by epigenetics play integral roles in the formation of new memories.However,as an important part of epigenetics,the function of chromatin remodeling in learning a...Gene transcription and new protein synthesis regulated by epigenetics play integral roles in the formation of new memories.However,as an important part of epigenetics,the function of chromatin remodeling in learning and memory has been less studied.Here,we showed that SMARCA5(SWI/SNF related,matrix-associated,actin-dependent regulator of chromatin,subfamily A,member 5),a critical chromatin remodeler,was responsible for hippocampus-dependent memory maintenance and neurogenesis.Using proteomics analysis,we found protein expression changes in the hippocampal dentate gyrus(DG)after the knockdown of SMARCA5 during contextual fear conditioning(CFC)memory maintenance in mice.Moreover,SMARCA5 was revealed to participate in CFC memory maintenance via modulating the proteins of metabolic pathways such as nucleoside diphosphate kinase-3(NME3)and aminoacylase 1(ACY1).This work is the first to describe the role of SMARCA5 in memory maintenance and to demonstrate the involvement of metabolic pathways regulated by SMARCA5 in learning and memory.展开更多
Local signaling events at synapses or axon terminals are communicated to the nucleus to elicit transcriptional responses,and thereby translate information about the external environment into internal neuronal represen...Local signaling events at synapses or axon terminals are communicated to the nucleus to elicit transcriptional responses,and thereby translate information about the external environment into internal neuronal representations.This retrograde signaling is critical to dendritic growth,synapse development,and neuronal plasticity.Here,we demonstrate that neuronal activity induces retrograde translocation and nuclear accumulation of endosomal adaptor APPL1.Disrupting the interaction of APPL1 with Importin ocl abolishes nuclear accumulation of APPL1,which in turn decreases the levels of histone acetylation.We further demonstrate that retrograde translocation of APPL1 is required for the regulation of gene transcription and then maintenance of hippocampal late-phase long-term potentiation.Thus,these results illustrate an APPLl-mediated pathway that contributes to the modulation of synaptic plasticity via coupling neuronal activity with chromatin remodeling.展开更多
The SWI/SNF chromatin remodeling complex utilizes the energy of ATP hydrolysis to facilitate chromatin access and plays essential roles in DNA-based events.Studies in animals,plants and fungi have uncovered sophistica...The SWI/SNF chromatin remodeling complex utilizes the energy of ATP hydrolysis to facilitate chromatin access and plays essential roles in DNA-based events.Studies in animals,plants and fungi have uncovered sophisticated regulatory mechanisms of this complex that govern development and various stress responses.In this review,we summarize the composition of SWI/SNF complex in eukaryotes and discuss multiple functions of the SWI/SNF complex in regulating gene transcription,mRNA splicing,and DNA damage response.Our review further highlights the importance of SWI/SNF complex in regulating plant immunity responses and fungal pathogenesis.Finally,the potentials in exploiting chromatin remodeling for management of crop disease are presented.展开更多
Subject Code:C05With the support from the National Natural Science Foundation of China,a collaborative study by the research teams led by Chen Zhucheng(陈柱成)and Li Xueming(李雪明)at the School of Life Sciences,Tsing...Subject Code:C05With the support from the National Natural Science Foundation of China,a collaborative study by the research teams led by Chen Zhucheng(陈柱成)and Li Xueming(李雪明)at the School of Life Sciences,Tsinghua University,recently reported their work,titled“Mechanism of chromatin remodeling revealed展开更多
The recent identification of cardiac progenitor cells （CPCs） provides a new paradigm for studying and treating heart disease. To realize the full potential of CPCs for therapeutic purposes, it is essential to unders...The recent identification of cardiac progenitor cells （CPCs） provides a new paradigm for studying and treating heart disease. To realize the full potential of CPCs for therapeutic purposes, it is essential to understand the genetic and epigenetic mechanisms guiding CPC differentiation into cardiomyocytes, smooth muscle, or endothelial cells. ATP-dependent chromatin remodelers mediate one critical epigenetic mechanism. These large multiprotein complexes open up chromatin to modulate transcription factor access to DNA. SWI/SNF, one of the major types of chromatin remodelers, plays a key role in various aspects of development （de la Serna et al., 2006; Wu et al., 2009）, including heart development and disease （Lickert et al., 2004; Wang et al., 2004; Huang et al., 2008; Stankunas et al., 2008; Hang et al., 2010）. In this review, we describe the specific function of various SWI/SNF components in cardiogenesis and cardiac progenitor cell （CPC） self-renewal and differentiation. We envision that a detailed understanding of the SWI/SNF in heart development and CPC formation and differentiation will generate novel insights into epigenetic mechanisms that govern CPC differentiation and may have significant implications in understanding and treating heart disease.展开更多
Pluripotent stem cells are able to both self-renew and generate undifferentiated cells for the formation of new tissues and organs. In higher plants, stem cells found in the shoot apical meristem （SAM） and the root ...Pluripotent stem cells are able to both self-renew and generate undifferentiated cells for the formation of new tissues and organs. In higher plants, stem cells found in the shoot apical meristem （SAM） and the root apical meristem （RAM） are origins of organogenesis occurring post-embryonically. It is important to understand how the regulation of stem cell fate is coordinated to enable the meristem to constantly generate different types of lateral organs. Much knowledge has accumulated on specific transcription factors controlling SAM and RAM activity. Here, we review recent evidences for a role of chromatin remodeling in the maintenance of stable expression states of transcription factor genes and the control of stem cell activity in Arabidopsis.展开更多
Wiedemann-Steiner syndrome(OMIM#605130)is a rare congenital malformation syndrome characterized by hypertrichosis cubiti associated with short stature;consistent facial features,including long eyelashes,thick or arche...Wiedemann-Steiner syndrome(OMIM#605130)is a rare congenital malformation syndrome characterized by hypertrichosis cubiti associated with short stature;consistent facial features,including long eyelashes,thick or arched eyebrows with a lateral flare,wide nasal bridge,and downslanting and vertically narrow palpebral fissures;mild to moderate intellectual disability;behavioral difficulties;and hypertrichosis on the back.It is caused by heterozygous pathogenic variants in KMT2A.This gene has an established role in histone methylation,which explains the overlap of Wiedemann-Steiner syndrome with other chromatinopathies,a heterogeneous group of syndromic conditions that share a common trigger:The disruption of one of the genes involved in chromatin modification,leading to dysfunction of the epigenetic machinery.展开更多
To explore the molecular mechanism of chromatin remodeling involved in the regulation of transcriptional activation of specific genes by a myogenic regulatory factor Myogenin, we used NIH3T3 fibroblasts with a stably ...To explore the molecular mechanism of chromatin remodeling involved in the regulation of transcriptional activation of specific genes by a myogenic regulatory factor Myogenin, we used NIH3T3 fibroblasts with a stably integrated Hl.l-GFP fusion protein to monitor histone HI movement directly by fluorescence recovery after photobleaching (FRAP) in living cells. The observation from FRAP experiments with myogenin transfected fibroblasts showed that the exchange rate of histone HI in chromatin was obviously increased, indicating that forced expression of exogenous Myogenin can induce chromatin remodeling. The hyper-acetylation of histones H3 and H4 from myogenin transfected fibroblasts was detected by triton-acid-urea (TAU)/SDS (2-D) electrophoresis and Western blot with specific antibodies against acetylated N-termini of histones H3 and H4. RT-PCR analysis indicated that the nAChR β-subunit gene was expressed in the transfected fibroblasts. These results suggest that the expression of exogenous Myogenin can induce chromatin remodeling and activate the transcription of Myogenin-targeted gene in non-muscle cells.展开更多
Eukaryotic chromatin consisting of nucleosomes connected by linker DNA is organized into higher order structures,which is facilitated by linker histone H1.Formation of chromatin compacts and protects the genome,but al...Eukaryotic chromatin consisting of nucleosomes connected by linker DNA is organized into higher order structures,which is facilitated by linker histone H1.Formation of chromatin compacts and protects the genome,but also hinders DNA transactions.Cells have evolved mechanisms to modify/remodel chromatin resulting in chromatin states suitable for genome functions.The high mobility group box(HMGB)proteins are non-histone chromatin architectural factors characterized by one or more HMGB motifs that bind DNA in a sequence nonspecific fashion.They play a major role in chromatin dynamics.The Saccharomyces cerevisiae(yeast hereafter)HMGB protein Hmo1 contains two HMGB motifs.However,unlike a canonical HMGB protein that has an acidic C-terminus,Hmo1 ends with a lysine rich,basic,C-terminus,resembling linker histone H1.Hmo1 exhibits characteristics of both HMGB proteins and linker histones in its multiple functions.For instance,Hmo1 promotes transcription by RNA polymerases I and II like canonical HMGB proteins but makes chromatin more compact/stable like linker histones.Recent studies have demonstrated that Hmo1 destabilizes/disrupts nucleosome similarly as other HMGB proteins in vitro and acts to maintain a common topological architecture of genes in yeast genome.This minireview reviews the functions of Hmo1 and the underlying mechanisms,highlighting recent discoveries.展开更多
Chlorophyll biosynthesis is critical for chloroplast development and photosynthesis in plants. Although reactions in the chlorophyll biosynthetic pathway have been largely known, little is known about the regu-latory ...Chlorophyll biosynthesis is critical for chloroplast development and photosynthesis in plants. Although reactions in the chlorophyll biosynthetic pathway have been largely known, little is known about the regu-latory mechanisms of this pathway. In this study, we found that the dark-grown knockout and knockdown mutants as well as RNA-interference transgenic seedlings of BRAHMA （BRM）, which encodes an SWI2/ SNF2 chromatin-remodeling ATPase, had iligher greening rates, accumulated less protochlorophyllide, and produced less reactive oxygen species than Arabidopsis wild-type plants did upon light exposure. The expression of NADPH：protochlorophyilide oxidoreductase A （PORA）, PORB, and PORC, which catalyze a key step in chlorophyll biosynthesis, was increased in the brm mutants. We found that BRM physically interacted with the bHLH transcription factor PHYTOCHRONIE-iNTERACTING FACTOR 1 （PIF1） through its N-terminal domains. Furthermore, we demonstrated that BRM was directly recruited to the cis-regula-tory regions of PORC, but not of PORA and PORB, at least partially in a PIF1-dependent manner and the level of histone H3 lysine 4 tri-methylation （H3K4me3） at PORC loci was increased in the brm mutant. Taken together, our data indicate that the chromatino-remodeling enzyme BRM modulates PORC expression through interacting with PIF1, providing a novel regulatory mechanism by which plants fine-tune chloro-phyll biosynthesis during the transition from heterotrophic to autotrophic growth.展开更多
Optimal response to drought is critical for plant survival and will affect biodiversity and crop performance during climate change. Mitotically heritable epigenetic or dynamic chromatin state changes have been implica...Optimal response to drought is critical for plant survival and will affect biodiversity and crop performance during climate change. Mitotically heritable epigenetic or dynamic chromatin state changes have been implicated in the plant response to the drought stress hormone abscisic acid （ABA）. The Arabidopsis SWI/SNF chromatin-remodeling ATPase BRAHMA （BRM） modulates response to ABA by preventing pre- mature activation of stress response pathways during germination. We show that core ABA signaling pathway components physically interact with BRM and post-translationally modify BRM by phosphoryla- tion/dephosphorylation. Genetic evidence suggests that BRM acts downstream of SnRK2.2/2.3 kinases, and biochemical studies identified phosphorylation sites in the C-terminal region of BRM at SnRK2 target sites that are evolutionarUy conserved. Finally, the phosphomimetic BRMs17s^D S1762D mutant displays ABA hypersensitivity. Prior studies showed that BRM resides at target loci in the ABA pathway in the presence and absence of the stimulus, but is only active in the absence of ABA. Our data suggest that SnRK2- dependent phosphorylation of BRM leads to its inhibition, and PP2CA-mediated dephosphorylation of BRM restores the ability of BRM to repress ABA response. These findings point to the presence of a rapid phosphorylation-based switch to control BRM activity; this property could be potentially harnessed to improve drought tolerance in plants.展开更多
Incorporation of the histone variant H2A.Z into nucleosomes by the SWR1 chromatin remodeling complex is a critical step in eukaryotic gene regulation. In Arabidopsis, SWRlc and H2A.Z have been shown to con- trol gene ...Incorporation of the histone variant H2A.Z into nucleosomes by the SWR1 chromatin remodeling complex is a critical step in eukaryotic gene regulation. In Arabidopsis, SWRlc and H2A.Z have been shown to con- trol gene expression underlying development and environmental responses. Although they have been implicated in defense, the specific roles of the complex subunits and H2A.Z in immunity are not well under- stood. In this study, we analyzed the roles of the SWRlc subunits, PHOTOPERIOD-INDEPENDENT EARLY FLOWERING1 （PIE1）, ACTIN-RELATED PROTEIN6 （ARP6）, and SWR1 COMPLEX 6 （SWC6）, as well as H2A.Z, in defense and gene regulation. We found that SWRlc components play different roles in resistance to different pathogens. Loss of PIE1 and SWC6 function as well as depletion of H2A.Z led to reduced basal resistance, while loss of ARP6 fucntion resulted in enhanced resistance. We found that mutations in PIE1 and SWC6 resulted in impaired effector-triggered immunity. Mutation in SWRlc components and H2A.Z also resulted in compromised jasmonic acid/ethylene-mediated immunity. Genome-wide expres- sion analyses similarly reveal distinct roles for H2A.Z and SWRlc components in gene regulation, and sug- gest a potential role for PIE1 in the regulation of the cross talk between defense signaling pathways. Our data show that although they are part of the same complex, Arabidopsis SWRlc components could have non-redundant functions in plant immunity and gene regulation.展开更多
基金supported by the National Natural Science Foundation of China(32172389)the Excellent Youth Foundation of Henan Province,China(232300421029)the Key Research and Development Project of Henan Province,China(221111112200)。
文摘The insect fat body is comparable to the liver and adipose tissue in vertebrates,and plays a pivotal role in energy metabolism,nutrient storage,and reproduction.During metamorphosis,the fat body is disassembled via programmed cell death and cell dissociation.After adult eclosion,the fat body is reconstructed either by repopulation from the remaining juvenile fat body cells or by differentiation from adult progenitor cells.This reconstruction is a prerequisite for initiating the extensive synthesis of vitellogenin(Vg),which is necessary for the maturation of eggs.Despite its significance,the underlying mechanisms of this reconstruction remain inadequately understood.Transcriptome analysis of the fat bodies from migratory locusts at 0-5 days post adult emergence revealed 79 genes associated with chromatin remodeling.Weighted gene co-expression network analysis indicated a positive correlation between chromatin remodeling and fat body reconstitution.Protein-protein interaction analysis revealed that brahma,which encodes the catalytic subunit of the SWI/SNF chromatin remodeling complex,is crucial for post-adult-eclosion fat body development.qRT-PCR analysis demonstrated that the levels of brahma mRNA in the fat body are progressively increased during the previtellogenic stage,then reach the peak and remain elevated in the vitellogenic phase.Furthermore,brahma is expressed in response to gonadotropic juvenile hormone(JH).Knockdown of brahma led to a marked reduction in Vg expression within the fat body,along with arrested ovarian growth.These findings shed light on the involvement of brahmamediated chromatin remodeling in JH-stimulated fat body reconstruction and reproduction of adult female locusts.
文摘Objective:To investigate the regulatory effects of acupuncture and moxibustion on chromatin remodeling complex core catalytic subunit of Brahma-related gene 1(Brg1),histone deacetylase(HDAC)3,HDAC9,and males absent on the first(MOF)in the colon tissue of rats with Crohn disease(CD).Methods:Using the random number table method,60 male Sprague-Dawley rats were divided into 5 groups,including a normal group,a model group,an acupuncture group,a medicinal cake-insulated moxibustion group,and an acupuncture-moxibustion group,with 12 rats in each group.CD rat models were prepared using 2,4,6-trinitrobenzene sulfonic acid(TNBS)in all groups except the normal group.The normal and model groups received no interventions.In the acupuncture group,rats were intervened with acupuncture at bilateral Zusanli(ST36)and Shangjuxu(ST37),20 min/session,once a day.The medicinal cake-insulated moxibustion group received medicinal cake-insulated moxibustion at Qihai(CV6)and bilateral Tianshu(ST25)with 2 cones per point per session,once a day.The acupuncture-moxibustion group received both acupuncture and moxibustion interventions simultaneously.Each intervention was performed for 10 consecutive days.Observations included general condition,disease activity,macroscopic damage,and pathological changes in the rat’s colon tissue.Realtime fluorescence quantitative polymerase chain reaction was used to measure the mRNA expression of chromatin remodeling-related enzymes Brg1,HDAC3,and HDAC9,while Western blotting detected the protein expression of Brg1,HDAC3,HDAC9,and MOF in rat’s colon tissue.Results:The model group showed significantly increased diarrhea score,occult blood score,macroscopic damage score of colon tissue,and colon macroscopic damage index(CMDI)score,as well as elevated mRNA expression levels of HDAC3 and HDAC9,protein expression levels of HDAC3,HDAC9,and MOF,and decreased mRNA and protein expression levels of Brg1 compared to the normal group(P<0.01).In contrast,compared to the model group,the diarrhea score,occult blood score,macroscopic damage score,CMDI score,mRNA expression levels of HDAC3 and HDAC9,and protein expression levels of HDAC3,HDAC9,and MOF were significantly reduced(P<0.05 or P<0.01),while the mRNA and protein expression levels of Brg1 were significantly increased(P<0.01)in the acupuncture group,the medicinal cake-insulated moxibustion group,and the acupuncture-moxibustion group.Conclusion:Both medicinal cake-insulated moxibustion and acupuncture,either used alone or in combination,can regulate the abnormal expression of chromatin remodeling-related enzymes Brg1,HDAC3,HDAC9,and MOF in the colon tissue,thus reducing colon inflammation in CD rats.
基金National Natural Science Foundation of China(82372663)Key Research and Development Program of Jiangxi Province(20232BBG70024)+1 种基金Key Research and Development Program of Yunnan Province(202302AA310024)Natural Science Foundation of Shandong Province(ZR2023LSW008)and the Faculty Resources Project of College of Life Sciences(Inner Mongolia University 2022−103).
文摘Tissue stem cells(TSCs),which reside in specialized tissues,constitute the major cell sources for tissue homeosta-sis and regeneration,and the contribution of transcriptional or epigenetic regulation of distinct biological pro-cesses in TSCs has been discussed in the past few decades.Meanwhile,ATP-dependent chromatin remodelers use the energy from ATP hydrolysis to remodel nucleosomes,thereby affecting chromatin dynamics and the regulation of gene expression programs in each cell type.However,the role of chromatin remodelers in tissue stem cell fate determination is less well understood.In this review,we systematically discuss recent advances in epigenetic control by chromatin remodelers of hematopoietic stem cells,intestinal epithelial stem cells,neural stem cells,and skin stem cells in their fate determination and highlight the importance of their essential role in tissue homeostasis,devel-opment,and regeneration.Moreover,the exploration of the molecular and cellular mechanisms of TSCs is crucial for advancing our understanding of tissue maintenance and for the discovery of novel therapeutic targets.
基金financially supported by grants from the National Natural Science Foundation of China(31970287,31800210,and 31625004)。
文摘Environmental stress from climate change and agricultural activity threatens global plant biodiversity as well as crop yield and quality.As sessile organisms,plants must maintain the integrity of their genomes and adjust gene expression to adapt to various environmental changes.In eukaryotes,nucleosomes are the basic unit of chromatin around which genomic DNA is packaged by condensation.To enable dynamic access to packaged DNA,eukaryotes have evolved Snf2(sucrose nonfermenting 2)family proteins as chromatin remodeling factors(CHRs)that modulate the position of nucleosomes on chromatin.During plant stress responses,CHRs are recruited to specific genomic loci,where they regulate the distribution or composition of nucleosomes,which in turn alters the accessibility of these loci to general transcription or DNA damage repair machinery.Moreover,CHRs interplay with other epigenetic mechanisms,including DNA methylation,histone modifications,and deposition of histone variants.CHRs are also involved in RNA processing at the posttranscriptional level.In this review,we discuss major advances in our understanding of the mechanisms by which CHRs function during plants’response to environmental stress.
基金supported by the grant from National Basic Research Program of China (973 Program 2012CB910503)
文摘The Imitation Switch （ISWI） type adenosine triphosphate （ATP）-dependent chromatin remodeling factors are conserved proteins in eukaryotes, and some of them are known to form stable remodeling complexes with members from a family of proteins, termed DDT-domain proteins. Although it is well documented that ISWIs play important roles in different biological processes in many eukaryotic species, the molecular basis for protein interactions in ISWI complexes has not been fully addressed. Here, we report the identification of interaction domains for both ISWI and DDT-domain proteins. By analyzing CHROMATIN REMODELING11 （CH R11） and RINGLET1 （RLT1）, an Arabidopsis thaliana ISWI （AtlSWI） and AtDDT-domain protein, respectively, we show that the SLIDE domain of CHR11 and the DDT domain together with an adjacent sequence of RLT1 are responsible for their binding. The Arabidopsis genome contains at least 12 genes that encode DDT-domain proteins, which could be grouped into five subfamilies based on the sequence similarity. The SLIDE domain of AtlSWI is able to bind members from different AtDDT subfamilies. Moreover, a human ISWI protein SNF2H is capable of binding AtDDT-domain proteins through its SLIDE domain, suggesting that binding to DDT-domain proteins is a conserved biochemical function for the SLIDE domain of ISWIs in eukaryotes.
基金supported by the National Natural Science Foundation of China(31830045,32025005)。
文摘Plant reproduction requires the coordinated development of both male and female reproductive organs.Jasmonic acid(JA)plays an essential role in stamen filament elongation.However,the mechanism by which the JA biosynthesis genes are regulated to promote stamen elongation remains unclear.Here,we show that the chromatin remodeling complex Imitation of Switch(ISWI)promotes stamen filament elongation by regulating JA biosynthesis.We show that AT-Rich Interacting Domain 5(ARID5)interacts with CHR11,CHR17,and RLT1,several known subunits of ISWI.Mutations in ARID5 and RLTs caused a reduced seed set due to greatly shortened stamen filaments.RNA-seq analyses reveal that the expression of key genes responsible for JA biosynthesis is significantly down-regulated in the arid5 and rlt mutants.Consistently,the JA levels are drastically decreased in both arid5 and rlt mutants.Chromatin immunoprecipitationquantitative PCR analyses further show that ARID5 is recruited to the chromatin of JA biosynthesis genes.Importantly,exogenous JA treatments can fully rescue the defects of stamen filament elongation in both arid5 and rlt mutants,leading to the partial recovery of fertility.Our results provide a clue how JA biosynthesisis positively regulated by the chromatin remodeling complex ISWI,thereby promoting stamen filament elongation in Arabidopsis.
基金We thank X.Sun and M.Jin for technical assistance.This work was supported by the National Natural Science Foundation of China(31570871,81571541,81771695,31770970,and 81770094)Program of Shanghai Chief Scientist of Medical and Health Subject(2018BR16)Shuguang Program sponsored by the Shanghai Education Development Foundation and Shanghai Municipal Education Commission(18SG33).
文摘IL-6 plays important and pleiotropic roles in infection and inflammatory diseases,and its production needs to be tightly regulated.However,the epigenetic mechanism underlying Il6 gene transcription remains to be fully elucidated.Here,we report that lysine-specific demethylase 2b(KDM2B),which demethylates H3K4me3 and H3K36me2,is required in macrophages and dendritic cells for the induction of IL-6 but not TNF-α,IL-1,and IFN-β.Compared to wild-type mice,KDM2B-deficient mice were more resistant to endotoxin shock and colitis,with a less severe inflammatory pathogenesis phenotype and decreased IL-6 production in sera.KDM2B selectively bound the Il6 promoter but did not alter histone demethylation;instead,KDM2B interacted with Brahma-related gene 1(Brg1),the core ATPase subunit of SWI/SNF chromatin remodeling complexes,to facilitate chromatin accessibility of the Il6 promoter.Furthermore,KDM2B directly recruited RNA Polymerase II to further initiate and promote Il6 transcription.Thus,our finding identifies a novel nonclassical function of KDM2B in gene-specific transcription initiation and enhancement of Il6 independent of its demethylase activity and adds new insight into the specific epigenetic modification mechanism of inflammatory immune responses.
基金supported by U.S. National Institutes of Health (Grant No. GM62484)
文摘Heterochromatin is characteristically more compact than chromatin is mediated by special histone modifications, euchromatin in the eukaryotic genome. The establishment of hetero- recruitment and propagation of heterochromatin specific proteins, as well as formation of special primary and high order structures of chromatin. Chromatin remodeling factors are ATPases that can alter the conformation and/or positioning of nucleosomes along DNA in an ATP-dependent manner. There is increasing evidence implicating chromatin remodeling activities in heterochromatin in various organisms ranging from yeasts to humans. Chromatin remodeling factors play roles in the establishment, maintenance and epigenetic inheritance of heterochromatin, but the underlying molecular mechanisms have just begun to be investigated.
基金supported by the Youth Program of the National Natural Science Foundation of China(32000788)Shandong Province Natural Science Foundation(ZR2019 BC097)+5 种基金Key Project from the National Natural Science Foundation of China(81830035)the Major program of National Natural Science Foundation of China(82090033)the Major Basic research program of Shandong Province Natural Science Foundation(ZR2019ZD35)The Major program of Technological innovation 2030"Brain science and brain-inspired research"(2021ZD0203002)Shandong Taishan Scholar Awardthe Fundamental Research Funds of Qingdao University.
文摘Gene transcription and new protein synthesis regulated by epigenetics play integral roles in the formation of new memories.However,as an important part of epigenetics,the function of chromatin remodeling in learning and memory has been less studied.Here,we showed that SMARCA5(SWI/SNF related,matrix-associated,actin-dependent regulator of chromatin,subfamily A,member 5),a critical chromatin remodeler,was responsible for hippocampus-dependent memory maintenance and neurogenesis.Using proteomics analysis,we found protein expression changes in the hippocampal dentate gyrus(DG)after the knockdown of SMARCA5 during contextual fear conditioning(CFC)memory maintenance in mice.Moreover,SMARCA5 was revealed to participate in CFC memory maintenance via modulating the proteins of metabolic pathways such as nucleoside diphosphate kinase-3(NME3)and aminoacylase 1(ACY1).This work is the first to describe the role of SMARCA5 in memory maintenance and to demonstrate the involvement of metabolic pathways regulated by SMARCA5 in learning and memory.
基金This work was supported by the National Natural Science Foundation of China(81671049 and 91732102 to S.Q.31900722 to Y.W.)+4 种基金Natural Science Foundation of Zhejiang Province for Distinguished Young Scholars(LR16C090001 to S.Q.)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2018PT31041)Fundamental Research Funds for the Central Universities of China(2019XZZX001-01-1A to S.Q.)the Chinese Ministry of Education Project 111 Program(B13026 to S.Q.)Key Realm R&D Program of Guangdong Province(2019B030335001).
文摘Local signaling events at synapses or axon terminals are communicated to the nucleus to elicit transcriptional responses,and thereby translate information about the external environment into internal neuronal representations.This retrograde signaling is critical to dendritic growth,synapse development,and neuronal plasticity.Here,we demonstrate that neuronal activity induces retrograde translocation and nuclear accumulation of endosomal adaptor APPL1.Disrupting the interaction of APPL1 with Importin ocl abolishes nuclear accumulation of APPL1,which in turn decreases the levels of histone acetylation.We further demonstrate that retrograde translocation of APPL1 is required for the regulation of gene transcription and then maintenance of hippocampal late-phase long-term potentiation.Thus,these results illustrate an APPLl-mediated pathway that contributes to the modulation of synaptic plasticity via coupling neuronal activity with chromatin remodeling.
基金supported by Science and Technology Project of Zhejiang Province(2018C02G2011110)China Postdoctoral Science Foundation(2021 M692849),National Natural Science Foundation of China(31930088)China Agriculture Research System of MOF and MARAC(CARS-3-1-29).
文摘The SWI/SNF chromatin remodeling complex utilizes the energy of ATP hydrolysis to facilitate chromatin access and plays essential roles in DNA-based events.Studies in animals,plants and fungi have uncovered sophisticated regulatory mechanisms of this complex that govern development and various stress responses.In this review,we summarize the composition of SWI/SNF complex in eukaryotes and discuss multiple functions of the SWI/SNF complex in regulating gene transcription,mRNA splicing,and DNA damage response.Our review further highlights the importance of SWI/SNF complex in regulating plant immunity responses and fungal pathogenesis.Finally,the potentials in exploiting chromatin remodeling for management of crop disease are presented.
文摘Subject Code:C05With the support from the National Natural Science Foundation of China,a collaborative study by the research teams led by Chen Zhucheng(陈柱成)and Li Xueming(李雪明)at the School of Life Sciences,Tsinghua University,recently reported their work,titled“Mechanism of chromatin remodeling revealed
文摘The recent identification of cardiac progenitor cells （CPCs） provides a new paradigm for studying and treating heart disease. To realize the full potential of CPCs for therapeutic purposes, it is essential to understand the genetic and epigenetic mechanisms guiding CPC differentiation into cardiomyocytes, smooth muscle, or endothelial cells. ATP-dependent chromatin remodelers mediate one critical epigenetic mechanism. These large multiprotein complexes open up chromatin to modulate transcription factor access to DNA. SWI/SNF, one of the major types of chromatin remodelers, plays a key role in various aspects of development （de la Serna et al., 2006; Wu et al., 2009）, including heart development and disease （Lickert et al., 2004; Wang et al., 2004; Huang et al., 2008; Stankunas et al., 2008; Hang et al., 2010）. In this review, we describe the specific function of various SWI/SNF components in cardiogenesis and cardiac progenitor cell （CPC） self-renewal and differentiation. We envision that a detailed understanding of the SWI/SNF in heart development and CPC formation and differentiation will generate novel insights into epigenetic mechanisms that govern CPC differentiation and may have significant implications in understanding and treating heart disease.
文摘Pluripotent stem cells are able to both self-renew and generate undifferentiated cells for the formation of new tissues and organs. In higher plants, stem cells found in the shoot apical meristem （SAM） and the root apical meristem （RAM） are origins of organogenesis occurring post-embryonically. It is important to understand how the regulation of stem cell fate is coordinated to enable the meristem to constantly generate different types of lateral organs. Much knowledge has accumulated on specific transcription factors controlling SAM and RAM activity. Here, we review recent evidences for a role of chromatin remodeling in the maintenance of stable expression states of transcription factor genes and the control of stem cell activity in Arabidopsis.
文摘Wiedemann-Steiner syndrome(OMIM#605130)is a rare congenital malformation syndrome characterized by hypertrichosis cubiti associated with short stature;consistent facial features,including long eyelashes,thick or arched eyebrows with a lateral flare,wide nasal bridge,and downslanting and vertically narrow palpebral fissures;mild to moderate intellectual disability;behavioral difficulties;and hypertrichosis on the back.It is caused by heterozygous pathogenic variants in KMT2A.This gene has an established role in histone methylation,which explains the overlap of Wiedemann-Steiner syndrome with other chromatinopathies,a heterogeneous group of syndromic conditions that share a common trigger:The disruption of one of the genes involved in chromatin modification,leading to dysfunction of the epigenetic machinery.
文摘To explore the molecular mechanism of chromatin remodeling involved in the regulation of transcriptional activation of specific genes by a myogenic regulatory factor Myogenin, we used NIH3T3 fibroblasts with a stably integrated Hl.l-GFP fusion protein to monitor histone HI movement directly by fluorescence recovery after photobleaching (FRAP) in living cells. The observation from FRAP experiments with myogenin transfected fibroblasts showed that the exchange rate of histone HI in chromatin was obviously increased, indicating that forced expression of exogenous Myogenin can induce chromatin remodeling. The hyper-acetylation of histones H3 and H4 from myogenin transfected fibroblasts was detected by triton-acid-urea (TAU)/SDS (2-D) electrophoresis and Western blot with specific antibodies against acetylated N-termini of histones H3 and H4. RT-PCR analysis indicated that the nAChR β-subunit gene was expressed in the transfected fibroblasts. These results suggest that the expression of exogenous Myogenin can induce chromatin remodeling and activate the transcription of Myogenin-targeted gene in non-muscle cells.
文摘Eukaryotic chromatin consisting of nucleosomes connected by linker DNA is organized into higher order structures,which is facilitated by linker histone H1.Formation of chromatin compacts and protects the genome,but also hinders DNA transactions.Cells have evolved mechanisms to modify/remodel chromatin resulting in chromatin states suitable for genome functions.The high mobility group box(HMGB)proteins are non-histone chromatin architectural factors characterized by one or more HMGB motifs that bind DNA in a sequence nonspecific fashion.They play a major role in chromatin dynamics.The Saccharomyces cerevisiae(yeast hereafter)HMGB protein Hmo1 contains two HMGB motifs.However,unlike a canonical HMGB protein that has an acidic C-terminus,Hmo1 ends with a lysine rich,basic,C-terminus,resembling linker histone H1.Hmo1 exhibits characteristics of both HMGB proteins and linker histones in its multiple functions.For instance,Hmo1 promotes transcription by RNA polymerases I and II like canonical HMGB proteins but makes chromatin more compact/stable like linker histones.Recent studies have demonstrated that Hmo1 destabilizes/disrupts nucleosome similarly as other HMGB proteins in vitro and acts to maintain a common topological architecture of genes in yeast genome.This minireview reviews the functions of Hmo1 and the underlying mechanisms,highlighting recent discoveries.
文摘Chlorophyll biosynthesis is critical for chloroplast development and photosynthesis in plants. Although reactions in the chlorophyll biosynthetic pathway have been largely known, little is known about the regu-latory mechanisms of this pathway. In this study, we found that the dark-grown knockout and knockdown mutants as well as RNA-interference transgenic seedlings of BRAHMA （BRM）, which encodes an SWI2/ SNF2 chromatin-remodeling ATPase, had iligher greening rates, accumulated less protochlorophyllide, and produced less reactive oxygen species than Arabidopsis wild-type plants did upon light exposure. The expression of NADPH：protochlorophyilide oxidoreductase A （PORA）, PORB, and PORC, which catalyze a key step in chlorophyll biosynthesis, was increased in the brm mutants. We found that BRM physically interacted with the bHLH transcription factor PHYTOCHRONIE-iNTERACTING FACTOR 1 （PIF1） through its N-terminal domains. Furthermore, we demonstrated that BRM was directly recruited to the cis-regula-tory regions of PORC, but not of PORA and PORB, at least partially in a PIF1-dependent manner and the level of histone H3 lysine 4 tri-methylation （H3K4me3） at PORC loci was increased in the brm mutant. Taken together, our data indicate that the chromatino-remodeling enzyme BRM modulates PORC expression through interacting with PIF1, providing a novel regulatory mechanism by which plants fine-tune chloro-phyll biosynthesis during the transition from heterotrophic to autotrophic growth.
文摘Optimal response to drought is critical for plant survival and will affect biodiversity and crop performance during climate change. Mitotically heritable epigenetic or dynamic chromatin state changes have been implicated in the plant response to the drought stress hormone abscisic acid （ABA）. The Arabidopsis SWI/SNF chromatin-remodeling ATPase BRAHMA （BRM） modulates response to ABA by preventing pre- mature activation of stress response pathways during germination. We show that core ABA signaling pathway components physically interact with BRM and post-translationally modify BRM by phosphoryla- tion/dephosphorylation. Genetic evidence suggests that BRM acts downstream of SnRK2.2/2.3 kinases, and biochemical studies identified phosphorylation sites in the C-terminal region of BRM at SnRK2 target sites that are evolutionarUy conserved. Finally, the phosphomimetic BRMs17s^D S1762D mutant displays ABA hypersensitivity. Prior studies showed that BRM resides at target loci in the ABA pathway in the presence and absence of the stimulus, but is only active in the absence of ABA. Our data suggest that SnRK2- dependent phosphorylation of BRM leads to its inhibition, and PP2CA-mediated dephosphorylation of BRM restores the ability of BRM to repress ABA response. These findings point to the presence of a rapid phosphorylation-based switch to control BRM activity; this property could be potentially harnessed to improve drought tolerance in plants.
文摘Incorporation of the histone variant H2A.Z into nucleosomes by the SWR1 chromatin remodeling complex is a critical step in eukaryotic gene regulation. In Arabidopsis, SWRlc and H2A.Z have been shown to con- trol gene expression underlying development and environmental responses. Although they have been implicated in defense, the specific roles of the complex subunits and H2A.Z in immunity are not well under- stood. In this study, we analyzed the roles of the SWRlc subunits, PHOTOPERIOD-INDEPENDENT EARLY FLOWERING1 （PIE1）, ACTIN-RELATED PROTEIN6 （ARP6）, and SWR1 COMPLEX 6 （SWC6）, as well as H2A.Z, in defense and gene regulation. We found that SWRlc components play different roles in resistance to different pathogens. Loss of PIE1 and SWC6 function as well as depletion of H2A.Z led to reduced basal resistance, while loss of ARP6 fucntion resulted in enhanced resistance. We found that mutations in PIE1 and SWC6 resulted in impaired effector-triggered immunity. Mutation in SWRlc components and H2A.Z also resulted in compromised jasmonic acid/ethylene-mediated immunity. Genome-wide expres- sion analyses similarly reveal distinct roles for H2A.Z and SWRlc components in gene regulation, and sug- gest a potential role for PIE1 in the regulation of the cross talk between defense signaling pathways. Our data show that although they are part of the same complex, Arabidopsis SWRlc components could have non-redundant functions in plant immunity and gene regulation.
