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Nature:周期性DNA甲基化影响转录活性

来源:Nature 2008-03-12 12:16

生物谷报道:最新研究表明基因的表达严格按照基因组的调节。表观遗传包括很多信息并没有出现在DNA序列之中,在发育过程中环境限制了一部分基因的表达。DNA序列中CpGs结构的甲基化对表观遗传的调节具有显著作用,它可以使染色体转录沉默。甲基化作用可以使基因组在细胞分裂过程中保持稳定。最近研究发现一种动力在人类细胞DNA甲基化过程中起到重大作用。人类雌性激素可作用于pS2/TFF1基因的启动子,通过调节甲基化和去甲基化影响基因表达。DNA甲基化同时通过脱氨出现在CpG和5mCpGs结构中。这种抑制作用不影响pS2基因启动子序列的甲基化和其后随序列的活性。CpGs结构启动子通过周期性的DNA甲基化状态调节转录产物使基因表达多样化。(生物谷    赵晨光)

生物谷推荐原始出处:

Nature 452, 45-50 (6 March 2008) | doi:10.1038/nature06544; Received 21 September 2007; Accepted 12 December 2007

Cyclical DNA methylation of a transcriptionally active promoter

Raphaël Métivier, Rozenn Gallais, Christophe Tiffoche, Christine Le Péron, Renata Z. Jurkowska, Richard P. Carmouche, David Ibberson, Peter Barath, Florence Demay, George Reid, Vladimir Benes, Albert Jeltsch, Frank Gannon& Gilles Salbert

Processes that regulate gene transcription are directly under the influence of the genome organization. The epigenome contains additional information that is not brought by DNA sequence, and generates spatial and functional constraints that complement genetic instructions. DNA methylation on CpGs constitutes an epigenetic mark generally correlated with transcriptionally silent condensed chromatin. Replication of methylation patterns by DNA methyltransferases maintains genome stability through cell division. Here we present evidence of an unanticipated dynamic role for DNA methylation in gene regulation in human cells. Periodic, strand-specific methylation/demethylation occurs during transcriptional cycling of the pS2/TFF1 gene promoter on activation by oestrogens. DNA methyltransferases exhibit dual actions during these cycles, being involved in CpG methylation and active demethylation of 5mCpGs through deamination. Inhibition of this process precludes demethylation of the pS2 gene promoter and its subsequent transcriptional activation. Cyclical changes in the methylation status of promoter CpGs may thus represent a critical event in transcriptional achievement.

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