DNA methylation,especially methylation of cytosine in eukaryotic organisms,has been implicated in gene regulation,genomic imprinting,the timing of DNA replication,and determination of chromatin structure.It was report...DNA methylation,especially methylation of cytosine in eukaryotic organisms,has been implicated in gene regulation,genomic imprinting,the timing of DNA replication,and determination of chromatin structure.It was reported that 6.5% of the whole cytosine residues in the nuclear DNA in展开更多
Cytosine bases of the nuclear genome in higher plants are often extensively methylated.Cytosine methylation has been implicated in the silencing of both transposable elements (TEs) and endogenous genes,and loss of m...Cytosine bases of the nuclear genome in higher plants are often extensively methylated.Cytosine methylation has been implicated in the silencing of both transposable elements (TEs) and endogenous genes,and loss of methylation may have severe functional consequences.The recent methylation profiling of the entire Arabidopsis genome has provided novel insights into the extent and pattern of cytosine methylation and its relationships with gene activity.In addition,the fresh studies also revealed the more dynamic nature of this epigenetic modification across plant development than previously believed.Cytosine methylation of gene promoter regions usually inhibits transcription,but methylation in coding regions (gene-body methylation) does not generally affect gene expression.Active demethylation (though probably act synergistically with passive loss of methylation) of promoters by the 5-methyl cytosine DNA glycosylase or DEMETER (DME) is required for the uni-parental expression of imprinting genes in endosperm,which is essential for seed viability.The opinion that cytosine methylation is indispensible for normal plant development has been reinforced by using single or combinations of diverse loss-of-function mutants for DNA methyltransferases,DNA glycosylases,components involved in siRNA biogenesis and chromatin remodeling factors.Patterns of cytosine methylation in plants are usually faithfully maintained across organismal generations by the concerted action of epigenetic inheritance and progressive correction of strayed patterns.However,some variant methylation patterns may escape from being corrected and hence produce novel epialleles in the affected somatic cells.This,coupled with the unique property of plants to produce germline cells late during development,may enable the newly acquired epialleles to be inherited to future generations,which if visible to selection may contribute to adaptation and evolution.展开更多
The thymine DNA glycosylase (TDG) is a multifunctional enzyme,which is essential for embryonic development.It mediates the base excision repair (BER) of G:T and G:U DNA mismatches arising from the deamination of...The thymine DNA glycosylase (TDG) is a multifunctional enzyme,which is essential for embryonic development.It mediates the base excision repair (BER) of G:T and G:U DNA mismatches arising from the deamination of 5-methyl cytosine (5-MeC) and cytosine,respectively.Recent studies have pointed at a role of TDG during the active demethylation of 5-MeC within CpG islands.TDG interacts with the histone acetylase CREB-binding protein (CBP) to activate CBP-dependent transcription.In addition,TDG also interacts with the retinoic acid receptor α (RARα),resulting in the activation of RARα target genes.Here we provide evidence for the existence of a functional ternary complex containing TDG,CBP and activated RARα.Using global transcriptome profiling,we uncover a coupling of de novo methylation-sensitive and RA-dependent transcription,which coincides with a significant subset of CBP target genes.The introduction of a point mutation in TDG,which neither affects overall protein structure nor BER activity,leads to a significant loss in ternary complex stability,resulting in the deregulation of RA targets involved in cellular networks associated with DNA replication,recombination and repair.We thus demonstrate for the first time a direct coupling of TDG's epigenomic and transcription regulatory function through ternary complexes with CBP and RARα.展开更多
文摘DNA methylation,especially methylation of cytosine in eukaryotic organisms,has been implicated in gene regulation,genomic imprinting,the timing of DNA replication,and determination of chromatin structure.It was reported that 6.5% of the whole cytosine residues in the nuclear DNA in
基金supported by the National Natural Science Foundation of China (No. 30870198 and 30870178)the Programme of Introducing Talents of Discipline to Universities of China (No. B07017)
文摘Cytosine bases of the nuclear genome in higher plants are often extensively methylated.Cytosine methylation has been implicated in the silencing of both transposable elements (TEs) and endogenous genes,and loss of methylation may have severe functional consequences.The recent methylation profiling of the entire Arabidopsis genome has provided novel insights into the extent and pattern of cytosine methylation and its relationships with gene activity.In addition,the fresh studies also revealed the more dynamic nature of this epigenetic modification across plant development than previously believed.Cytosine methylation of gene promoter regions usually inhibits transcription,but methylation in coding regions (gene-body methylation) does not generally affect gene expression.Active demethylation (though probably act synergistically with passive loss of methylation) of promoters by the 5-methyl cytosine DNA glycosylase or DEMETER (DME) is required for the uni-parental expression of imprinting genes in endosperm,which is essential for seed viability.The opinion that cytosine methylation is indispensible for normal plant development has been reinforced by using single or combinations of diverse loss-of-function mutants for DNA methyltransferases,DNA glycosylases,components involved in siRNA biogenesis and chromatin remodeling factors.Patterns of cytosine methylation in plants are usually faithfully maintained across organismal generations by the concerted action of epigenetic inheritance and progressive correction of strayed patterns.However,some variant methylation patterns may escape from being corrected and hence produce novel epialleles in the affected somatic cells.This,coupled with the unique property of plants to produce germline cells late during development,may enable the newly acquired epialleles to be inherited to future generations,which if visible to selection may contribute to adaptation and evolution.
基金funded by the Centre National de la Recherche Scientifique(CNRS)and the Genopole Evry
文摘The thymine DNA glycosylase (TDG) is a multifunctional enzyme,which is essential for embryonic development.It mediates the base excision repair (BER) of G:T and G:U DNA mismatches arising from the deamination of 5-methyl cytosine (5-MeC) and cytosine,respectively.Recent studies have pointed at a role of TDG during the active demethylation of 5-MeC within CpG islands.TDG interacts with the histone acetylase CREB-binding protein (CBP) to activate CBP-dependent transcription.In addition,TDG also interacts with the retinoic acid receptor α (RARα),resulting in the activation of RARα target genes.Here we provide evidence for the existence of a functional ternary complex containing TDG,CBP and activated RARα.Using global transcriptome profiling,we uncover a coupling of de novo methylation-sensitive and RA-dependent transcription,which coincides with a significant subset of CBP target genes.The introduction of a point mutation in TDG,which neither affects overall protein structure nor BER activity,leads to a significant loss in ternary complex stability,resulting in the deregulation of RA targets involved in cellular networks associated with DNA replication,recombination and repair.We thus demonstrate for the first time a direct coupling of TDG's epigenomic and transcription regulatory function through ternary complexes with CBP and RARα.