DNA cytosine methylation confers stable epigenetic silencing in plants and many animals.However,the mechanisms underlying DNA methylation-mediated genomic silencing are not fully understood.We conducted a forward gene...DNA cytosine methylation confers stable epigenetic silencing in plants and many animals.However,the mechanisms underlying DNA methylation-mediated genomic silencing are not fully understood.We conducted a forward genetic screen for cellular factors required for the silencing of a heavily methylated p35S:NPTII transgene in the Arabidopsis thaliana rdm1-1 mutant background,which led to the identification of a Hsp20 family protein,RDS1(rdm1-1 suppressor 1).Loss-of-function mutations in RDS1 released the silencing of the p35S::NPTII transgene in rdm1-1 mutant plants,without changing the DNA methylation state of the transgene.Protein interaction analyses suggest that RDS1 exists in a protein complex consisting of the methyl-DNA binding domain proteins MBD5 and MBD6,two other Hsp20 family proteins,RDS2 and IDM3,a Hsp40/DNAJ family protein,and a Hsp70 family protein.Like rds1 mutations,mutations in RDS2,MBD5,or MBD6 release the silencing of the transgene in the rdm1 mutant background.Our results suggest that Hsp20,Hsp40,and Hsp70 proteins may form a complex that is recruited to some genomic regions with DNA methylation by methyl-DNA binding proteins to regulate the state of silencing of these regions.展开更多
Subject Code:C02With the support by the Chinese Academy of Sciences(CAS),the research team of Plant Environmental Epigenetics led by Prof.He Yuehui(何跃辉)at the Shanghai Center for Plant Stress Biology,CAS and CAS Ce...Subject Code:C02With the support by the Chinese Academy of Sciences(CAS),the research team of Plant Environmental Epigenetics led by Prof.He Yuehui(何跃辉)at the Shanghai Center for Plant Stress Biology,CAS and CAS Center for Excellence of Molecular Plant Sciences,discovered a molecular epigenetic mechanism underlying how winter cold enables plants to flower in spring,which was published in Nature Genetics(2016,48:1527—1534).展开更多
Global prophylactic vaccination programmes have helped to curb new hepatitis B virus(HBV)infections.However,it is estimated that nearly 300 million people are chronically infected and have a high risk of developing he...Global prophylactic vaccination programmes have helped to curb new hepatitis B virus(HBV)infections.However,it is estimated that nearly 300 million people are chronically infected and have a high risk of developing hepatocellular carcinoma.As such,HBV remains a serious health priority and the development of novel curative therapeutics is urgently needed.Chronic HBV infection has been attributed to the persistence of the covalently closed circular DNA(cccDNA)which establishes itself as a minichromosome in the nucleus of hepatocytes.As the viral transcription intermediate,the cccDNA is responsible for producing new virions and perpetuating infection.HBV is dependent on various host factors for cccDNA formation and the minichromosome is amenable to epigenetic modifications.Two HBV proteins,X(HBx)and core(HBc)promote viral replication by modulating the cccDNA epigenome and regulating host cell responses.This includes viral and host gene expression,chromatin remodeling,DNA methylation,the antiviral immune response,apoptosis,and ubiquitination.Elimination of the cccDNA minichromosome would result in a sterilizing cure;however,this may be difficult to achieve.Epigenetic therapies could permanently silence the cccDNA minichromosome and promote a functional cure.This review explores the cccDNA epigenome,how host and viral factors influence transcription,and the recent epigenetic therapies and epigenome engineering approaches that have been described.展开更多
Cancer cells show characteristic alterations in DNA methylation patterns. Aberrant CpG methylation of specificpromoters results in inactivation of tumor suppressor genes and therefore plays an important role in carcin...Cancer cells show characteristic alterations in DNA methylation patterns. Aberrant CpG methylation of specificpromoters results in inactivation of tumor suppressor genes and therefore plays an important role in carcinogenesis. Thep53-regulated gene 14-3-3σ undergoes frequent epigenetic silencing in several types of cancer, including carcinoma ofthe breast, prostate, and skin, suggesting that the loss of 14-3-3σ expression may be causally involved in tumor progression.Functional studies demonstrated that 14-3-3σ is involved in cell-cycle control and prevents the accumulation of chro-mosomal damage. The recent identification of novel 14-3-3σ-associated proteins by a targeted proteomics approachimplies that 14-3-3σ regulates diverse cellular processes, which may become deregulated after silencing of 14-3-3σexpression in cancer cells.展开更多
Transposable elements(TEs)regularly capture fragments of genes.When the host silences these TEs,siRNAs homologous to the captured regions may also target the genes.This epigenetic crosstalk establishes an intragenomic...Transposable elements(TEs)regularly capture fragments of genes.When the host silences these TEs,siRNAs homologous to the captured regions may also target the genes.This epigenetic crosstalk establishes an intragenomic conflict:silencing the TEs has the cost of silencing the genes.If genes are important,however,natural selection may maintain function by moderating the silencing response,which may also advantage the TEs.In this study,we examined this model by focusing on Helitrons,Pack-MULEs,and Sirevirus LTR retrotransposons in the maize genome.We documented 1263 TEs containing exon fragments from 1629 donor genes.Consistent with epigenetic conflict,donor genes mapped more siRNAs and were more methylated than genes with no evidence of capture.However,these patterns differed between syntelog versus translocated donor genes.Syntelogs appeared to maintain function,as measured by gene expression,consistent with moderation of silencing for functionally important genes.Epigenetic marks did not spread beyond their captured regions and 24nt crosstalk siRNAs were linked with CHH methylation.Translocated genes,in contrast,bore the signature of silencing.They were highly methylated and less expressed,but also overrepresented among donor genes and located away from chromosomal arms,which suggests a link between capture and gene movement.Splitting genes into potential functional categories based on evolutionary constraint supported the synteny-based findings.TE families captured genes in different ways,but the evidence for their advantage was generally less obvious;nevertheless,TEs with captured fragments were older,mapped fewer siRNAs,and were slightly less methylated than TEs without captured fragments.Collectively,our results argue that TE capture triggers an intragenomic conflict that may not affect the function of important genes but may lead to the pseudogenization of less-constrained genes.展开更多
Flowering plant （angiosperm） genomes are exceptional in their variability with respect to genome size, ploidy, chromosome number, gene content, and gene arrangement. Gene movement, although observed in some of the e...Flowering plant （angiosperm） genomes are exceptional in their variability with respect to genome size, ploidy, chromosome number, gene content, and gene arrangement. Gene movement, although observed in some of the earliest plant genome comparisons, has been relatively underinvestigated. We present here- in a description of several interesting properties of plant gene and genome structure that are pertinent to the successful movement of a gene to a new location. These considerations lead us to propose a model that can explain the frequent success of plant gene mobility, namely that Small Insulated Genes Move Around （SlGMAR）. The SIGMAR model is then compared with known processes for gene mobilization, and predic- tions of the SIGMAR model are formulated to encourage future experimentation. The overall results indicate that the frequent gene movement in angiosperm genomes is partly an outcome of the unusual properties of angiosperm genes, especially their small size and insulation from epigenetic silencing.展开更多
基金This work was supported by the Strategic Priority Research Program(grant XDB27040101 to J.-K.Z.)of the Chinese Academy of Sciences,and the Key Research and Development Plan of Shaanxi Province(grant No.2020ZDLNY01-03 to X.Z.).
文摘DNA cytosine methylation confers stable epigenetic silencing in plants and many animals.However,the mechanisms underlying DNA methylation-mediated genomic silencing are not fully understood.We conducted a forward genetic screen for cellular factors required for the silencing of a heavily methylated p35S:NPTII transgene in the Arabidopsis thaliana rdm1-1 mutant background,which led to the identification of a Hsp20 family protein,RDS1(rdm1-1 suppressor 1).Loss-of-function mutations in RDS1 released the silencing of the p35S::NPTII transgene in rdm1-1 mutant plants,without changing the DNA methylation state of the transgene.Protein interaction analyses suggest that RDS1 exists in a protein complex consisting of the methyl-DNA binding domain proteins MBD5 and MBD6,two other Hsp20 family proteins,RDS2 and IDM3,a Hsp40/DNAJ family protein,and a Hsp70 family protein.Like rds1 mutations,mutations in RDS2,MBD5,or MBD6 release the silencing of the transgene in the rdm1 mutant background.Our results suggest that Hsp20,Hsp40,and Hsp70 proteins may form a complex that is recruited to some genomic regions with DNA methylation by methyl-DNA binding proteins to regulate the state of silencing of these regions.
文摘Subject Code:C02With the support by the Chinese Academy of Sciences(CAS),the research team of Plant Environmental Epigenetics led by Prof.He Yuehui(何跃辉)at the Shanghai Center for Plant Stress Biology,CAS and CAS Center for Excellence of Molecular Plant Sciences,discovered a molecular epigenetic mechanism underlying how winter cold enables plants to flower in spring,which was published in Nature Genetics(2016,48:1527—1534).
文摘Global prophylactic vaccination programmes have helped to curb new hepatitis B virus(HBV)infections.However,it is estimated that nearly 300 million people are chronically infected and have a high risk of developing hepatocellular carcinoma.As such,HBV remains a serious health priority and the development of novel curative therapeutics is urgently needed.Chronic HBV infection has been attributed to the persistence of the covalently closed circular DNA(cccDNA)which establishes itself as a minichromosome in the nucleus of hepatocytes.As the viral transcription intermediate,the cccDNA is responsible for producing new virions and perpetuating infection.HBV is dependent on various host factors for cccDNA formation and the minichromosome is amenable to epigenetic modifications.Two HBV proteins,X(HBx)and core(HBc)promote viral replication by modulating the cccDNA epigenome and regulating host cell responses.This includes viral and host gene expression,chromatin remodeling,DNA methylation,the antiviral immune response,apoptosis,and ubiquitination.Elimination of the cccDNA minichromosome would result in a sterilizing cure;however,this may be difficult to achieve.Epigenetic therapies could permanently silence the cccDNA minichromosome and promote a functional cure.This review explores the cccDNA epigenome,how host and viral factors influence transcription,and the recent epigenetic therapies and epigenome engineering approaches that have been described.
文摘Cancer cells show characteristic alterations in DNA methylation patterns. Aberrant CpG methylation of specificpromoters results in inactivation of tumor suppressor genes and therefore plays an important role in carcinogenesis. Thep53-regulated gene 14-3-3σ undergoes frequent epigenetic silencing in several types of cancer, including carcinoma ofthe breast, prostate, and skin, suggesting that the loss of 14-3-3σ expression may be causally involved in tumor progression.Functional studies demonstrated that 14-3-3σ is involved in cell-cycle control and prevents the accumulation of chro-mosomal damage. The recent identification of novel 14-3-3σ-associated proteins by a targeted proteomics approachimplies that 14-3-3σ regulates diverse cellular processes, which may become deregulated after silencing of 14-3-3σexpression in cancer cells.
基金A.M.is supported by an EMBO Postdoctoral Fellowship ALTF 775-2017 and by HFSPO Fellowship LT000496/2018-LD.K.S.is supported by a Postdoctoral Fellowship from the National Science Foundation(NSF)Plant Genome Research Program(1609024)+1 种基金B.S.G.is supported by an NSF grant 1655808A.B.is supported by The Royal Society(award nos.UF160222 and RGF/R1/180006).
文摘Transposable elements(TEs)regularly capture fragments of genes.When the host silences these TEs,siRNAs homologous to the captured regions may also target the genes.This epigenetic crosstalk establishes an intragenomic conflict:silencing the TEs has the cost of silencing the genes.If genes are important,however,natural selection may maintain function by moderating the silencing response,which may also advantage the TEs.In this study,we examined this model by focusing on Helitrons,Pack-MULEs,and Sirevirus LTR retrotransposons in the maize genome.We documented 1263 TEs containing exon fragments from 1629 donor genes.Consistent with epigenetic conflict,donor genes mapped more siRNAs and were more methylated than genes with no evidence of capture.However,these patterns differed between syntelog versus translocated donor genes.Syntelogs appeared to maintain function,as measured by gene expression,consistent with moderation of silencing for functionally important genes.Epigenetic marks did not spread beyond their captured regions and 24nt crosstalk siRNAs were linked with CHH methylation.Translocated genes,in contrast,bore the signature of silencing.They were highly methylated and less expressed,but also overrepresented among donor genes and located away from chromosomal arms,which suggests a link between capture and gene movement.Splitting genes into potential functional categories based on evolutionary constraint supported the synteny-based findings.TE families captured genes in different ways,but the evidence for their advantage was generally less obvious;nevertheless,TEs with captured fragments were older,mapped fewer siRNAs,and were slightly less methylated than TEs without captured fragments.Collectively,our results argue that TE capture triggers an intragenomic conflict that may not affect the function of important genes but may lead to the pseudogenization of less-constrained genes.
文摘Flowering plant （angiosperm） genomes are exceptional in their variability with respect to genome size, ploidy, chromosome number, gene content, and gene arrangement. Gene movement, although observed in some of the earliest plant genome comparisons, has been relatively underinvestigated. We present here- in a description of several interesting properties of plant gene and genome structure that are pertinent to the successful movement of a gene to a new location. These considerations lead us to propose a model that can explain the frequent success of plant gene mobility, namely that Small Insulated Genes Move Around （SlGMAR）. The SIGMAR model is then compared with known processes for gene mobilization, and predic- tions of the SIGMAR model are formulated to encourage future experimentation. The overall results indicate that the frequent gene movement in angiosperm genomes is partly an outcome of the unusual properties of angiosperm genes, especially their small size and insulation from epigenetic silencing.
