Background and Aims:Hepatitis B virus(HBV)reactivation is commonly observed in individuals with chronic HBV infection undergoing antineoplastic drug therapy.Paclitaxel(PTX)treatment has been identified as a potential ...Background and Aims:Hepatitis B virus(HBV)reactivation is commonly observed in individuals with chronic HBV infection undergoing antineoplastic drug therapy.Paclitaxel(PTX)treatment has been identified as a potential trigger for HBV reactivation.This study aimed to uncover the mechanisms of PTX-induced HBV reactivation in vitro and in vivo,which may inform new strategies for HBV antiviral treatment.Methods:The impact of PTX on HBV replication was assessed through various methods including enzyme-linked immunosorbent assay,dual-luciferase reporter assay,quantitative real-time PCR,chromatin immunoprecipitation,and immunohistochemical staining.Transcriptome sequencing and 16S rRNA sequencing were employed to assess alterations in the transcriptome and microbial diversity in PTX-treated HBV transgenic mice.Results:PTX enhanced the levels of HBV 3.5-kb mRNA,HBV DNA,HBeAg,and HBsAg both in vitro and in vivo.PTX also promoted the activity of the HBV core promoter and transcription factor AP-1.Inhibition of AP-1 gene expression markedly suppressed PTX-induced HBV reactivation.Transcriptome sequencing revealed that PTX activated the immune-related signaling networks such as IL-17,NF-κB,and MAPK signaling pathways,with the pivotal common key molecule being AP-1.The 16S rRNA sequencing revealed that PTX induced dysbiosis of gut microbiota.Conclusions:PTX-induced HBV reactivation was likely a synergistic outcome of immune suppression and direct stimulation of HBV replication through the enhancement of HBV core promoter activity mediated by the transcription factor AP-1.These findings propose a novel molecular mechanism,underscoring the critical role of AP-1 in PTX-induced HBV reactivation.展开更多
The complexity of the epigenome landscape and transcriptional regulation is significantly increased during plant polyploidization,which drives genome evolution and contributes to the increased adaptability to diverse ...The complexity of the epigenome landscape and transcriptional regulation is significantly increased during plant polyploidization,which drives genome evolution and contributes to the increased adaptability to diverse environments.However,a comprehensive epigenome map of Brassica napus is still unavailable.In this study,we performed integrative analysis of five histone modifications,RNA polymerase Ⅱ CCU-pancy,DNA methylation,and transcriptomes in two B.napus lines(2063A and B409),and established global maps of regulatory elements,chromatin states,and their dynamics for the whole genome(including the An and Cn subgenomes)in four tissue types(young leaf,flower bud,silique,and root)of these two lines.Approximately 65.8% of the genome was annotated with different epigenomic signals.Compared with the Cn subgenome,the An subgenome possesses a higher level of active epigenetic marks and lower level of repressive epigenetic marks.Genes from subgenome-unique regions contribute to the major differences between the An and Cn subgenomes.Asymmetric histone modifications between homeologous gene pairs reflect their biased expression patterns.We identified a novel bivalent chromatin state(with H3K4me1 and H3K27me3)in B.napus that is associated with tissue-specific gene expression.Furthermore,we observed that different types of duplicated genes have discrepant patterns of histone modification and DNA methylation levels.Collectively,our findings provide a valuable epigenetic resource for allopolyploid plants.展开更多
基金This research received financial support from various sources including the Innovation and Development Joint Fund of Chongqing Natural Science Foundation(Grant number CSTB2023NSCQ-LZX0099)Chongqing Science and Health Joint Medical High-end Talent Project(Grant No.2022GDRC012)+3 种基金Chongqing Biomedical R&D Major Special Project(Grant No.CSTB2022TIAD-STX0013)Science and Technology Research Program of Chongqing Municipal Education Commission(Grant No.KJZD-K202100402)CQMU Program for Youth Innovation in Future Medicine(Grant No.W0073)the Southwest Medical University and Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University Joint Project(Grant No.2020XYLH-021).
文摘Background and Aims:Hepatitis B virus(HBV)reactivation is commonly observed in individuals with chronic HBV infection undergoing antineoplastic drug therapy.Paclitaxel(PTX)treatment has been identified as a potential trigger for HBV reactivation.This study aimed to uncover the mechanisms of PTX-induced HBV reactivation in vitro and in vivo,which may inform new strategies for HBV antiviral treatment.Methods:The impact of PTX on HBV replication was assessed through various methods including enzyme-linked immunosorbent assay,dual-luciferase reporter assay,quantitative real-time PCR,chromatin immunoprecipitation,and immunohistochemical staining.Transcriptome sequencing and 16S rRNA sequencing were employed to assess alterations in the transcriptome and microbial diversity in PTX-treated HBV transgenic mice.Results:PTX enhanced the levels of HBV 3.5-kb mRNA,HBV DNA,HBeAg,and HBsAg both in vitro and in vivo.PTX also promoted the activity of the HBV core promoter and transcription factor AP-1.Inhibition of AP-1 gene expression markedly suppressed PTX-induced HBV reactivation.Transcriptome sequencing revealed that PTX activated the immune-related signaling networks such as IL-17,NF-κB,and MAPK signaling pathways,with the pivotal common key molecule being AP-1.The 16S rRNA sequencing revealed that PTX induced dysbiosis of gut microbiota.Conclusions:PTX-induced HBV reactivation was likely a synergistic outcome of immune suppression and direct stimulation of HBV replication through the enhancement of HBV core promoter activity mediated by the transcription factor AP-1.These findings propose a novel molecular mechanism,underscoring the critical role of AP-1 in PTX-induced HBV reactivation.
基金This work was financially supported by the National Natural Science Foundation of China(31930032,31701163,31771422,and 31771402)the National Key Research and Development Program of China(2016YFD0101300 and 2018YFC1604000)+3 种基金the China Postdoctoral Science Foundation(2017M612479)the Fundamental Research Funds for the Central Universities(2662018py033)the open funds of the National Key Laboratory of Crop Genetic Improvement(ZK201906)the Program for Modern Agricultural Industrial Technology System of China(grant no.CARS-12).
文摘The complexity of the epigenome landscape and transcriptional regulation is significantly increased during plant polyploidization,which drives genome evolution and contributes to the increased adaptability to diverse environments.However,a comprehensive epigenome map of Brassica napus is still unavailable.In this study,we performed integrative analysis of five histone modifications,RNA polymerase Ⅱ CCU-pancy,DNA methylation,and transcriptomes in two B.napus lines(2063A and B409),and established global maps of regulatory elements,chromatin states,and their dynamics for the whole genome(including the An and Cn subgenomes)in four tissue types(young leaf,flower bud,silique,and root)of these two lines.Approximately 65.8% of the genome was annotated with different epigenomic signals.Compared with the Cn subgenome,the An subgenome possesses a higher level of active epigenetic marks and lower level of repressive epigenetic marks.Genes from subgenome-unique regions contribute to the major differences between the An and Cn subgenomes.Asymmetric histone modifications between homeologous gene pairs reflect their biased expression patterns.We identified a novel bivalent chromatin state(with H3K4me1 and H3K27me3)in B.napus that is associated with tissue-specific gene expression.Furthermore,we observed that different types of duplicated genes have discrepant patterns of histone modification and DNA methylation levels.Collectively,our findings provide a valuable epigenetic resource for allopolyploid plants.
