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细胞定向分化过程中的DNA甲基化动态变化

DNA methylation dynamics in cellular commitment and differentiation.

作者信息

Suelves Mònica, Carrió Elvira, Núñez-Álvarez Yaiza, Peinado Miguel A

出版信息

Brief Funct Genomics. 2016 Nov;15(6):443-453. doi: 10.1093/bfgp/elw017. Epub 2016 Jun 8.

DOI:10.1093/bfgp/elw017
PMID:27416614
Abstract

DNA methylation is an essential epigenetic modification for mammalian development and is crucial for the establishment and maintenance of cellular identity. Traditionally, DNA methylation has been considered as a permanent repressive epigenetic mark. However, the application of genome-wide approaches has allowed the analysis of DNA methylation in different genomic contexts, revealing a more dynamic regulation than originally thought, as active DNA methylation and demethylation occur during cell fate commitment and terminal differentiation. Recent data provide insights into the contribution of different epigenetic factors, and DNA methylation in particular, to the establishment of cellular memory during embryonic development and the modulation of cell type-specific gene regulation programs to ensure proper differentiation. This review summarizes published data regarding DNA methylation changes along lineage specification and differentiation programs. We also discuss the current knowledge about DNA methylation alterations occurring in physiological and pathological conditions such as aging and cancer.

摘要

DNA甲基化是哺乳动物发育过程中一种重要的表观遗传修饰,对于细胞特性的建立和维持至关重要。传统上,DNA甲基化一直被视为一种永久性的抑制性表观遗传标记。然而,全基因组方法的应用使得在不同基因组背景下对DNA甲基化进行分析成为可能,揭示出其调控比原先认为的更加动态,因为在细胞命运决定和终末分化过程中会发生主动DNA甲基化和去甲基化。最近的数据为不同表观遗传因子,特别是DNA甲基化,在胚胎发育过程中对细胞记忆建立的贡献以及对细胞类型特异性基因调控程序的调节以确保正常分化提供了见解。本综述总结了已发表的关于沿谱系特化和分化程序的DNA甲基化变化的数据。我们还讨论了目前关于在衰老和癌症等生理和病理条件下发生的DNA甲基化改变的知识。

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