DNA 甲基化与细胞身份的维持。

DNA methylation and the preservation of cell identity.

机构信息

Australian Research Council Centre of Excellence in Plant Energy Biology, University of Western Australia, Perth, Western Australia, Australia; Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.

Australian Research Council Centre of Excellence in Plant Energy Biology, University of Western Australia, Perth, Western Australia, Australia; Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia.

出版信息

Curr Opin Genet Dev. 2017 Oct;46:9-14. doi: 10.1016/j.gde.2017.06.007. Epub 2017 Jun 24.

DOI:10.1016/j.gde.2017.06.007

PMID:28651214

Abstract

DNA methylation is a major epigenetic modification of vertebrate genomes that is mostly associated with transcriptional repression. During embryogenesis, DNA methylation together with other epigenetic factors plays an essential role in selecting and maintaining cell identity. Recent technological advances are now allowing for the exploration of this mark at unprecedented resolution. This has resulted in a wealth of studies describing the developmental roles of DNA methylation in various vertebrate model systems. It is now evident that in certain contexts DNA methylation can act as a key regulator of cell identity establishment, whereas in many other cases the quantity of DNA methylation will merely reflect other upstream regulatory changes. For example, a number of studies have indicated that DNA methylation might be dispensable for pluripotency stages of embryonic development. Nevertheless, targeted deposition and removal of DNA methylation by DNMTs and TET proteins, respectively, appears to be required for vertebrate gastrulation. Here we review the roles of DNA methylation in the establishment and maintenance of cell identity during development, with a special emphasis on insights obtained from in vivo studies.

摘要

DNA 甲基化是脊椎动物基因组的一种主要表观遗传修饰，主要与转录抑制有关。在胚胎发生过程中，DNA 甲基化与其他表观遗传因子一起，在选择和维持细胞身份方面发挥着重要作用。最近的技术进步现在允许以前所未有的分辨率探索这种标记。这导致了大量的研究描述了 DNA 甲基化在各种脊椎动物模型系统中的发育作用。现在很明显，在某些情况下，DNA 甲基化可以作为细胞身份建立的关键调节剂，而在许多其他情况下，DNA 甲基化的数量仅仅反映了其他上游调节变化。例如，一些研究表明，DNA 甲基化对于胚胎发育的多能性阶段可能是可有可无的。然而，DNMT 和 TET 蛋白分别靶向 DNA 甲基化的沉积和去除，似乎是脊椎动物原肠胚形成所必需的。在这里，我们综述了 DNA 甲基化在发育过程中建立和维持细胞身份中的作用，特别强调了从体内研究中获得的见解。