Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Curr Top Dev Biol. 2013;104:243-91. doi: 10.1016/B978-0-12-416027-9.00008-5.
Proper development of an embryo requires tightly controlled expression of specific sets of genes. In order to generate all the lineages of the adult, populations of pluripotent embryonic stem cells differentiate and activate specific transcriptional programs whereas others are shutdown. The role of transcription factors is obvious in promoting expression of such developmental genes; however maintenance of specific states throughout cell division needs additional mechanisms. Indeed, the nucleoprotein complex of DNA and histones, the chromatin, can act as a facilitator or barrier to transcription depending on its configuration. Chromatin-modifying enzymes regulate accessibility of DNA by establishing specific sets of chromatin, which will be either permissive or repressive to transcription. In this review, we will describe the H3K9/HP1 and Polycomb pathways, which mediate transcriptional repression by modifying chromatin. We discuss how these two major epigenetic silencing modes are dynamically regulated and how they contribute to the early steps of embryo development.
胚胎的正常发育需要严格控制特定基因的表达。为了产生成体的所有谱系,多能胚胎干细胞群体分化并激活特定的转录程序,而其他程序则关闭。转录因子在促进此类发育基因的表达方面起着明显的作用;然而,在细胞分裂过程中保持特定的状态还需要其他机制。事实上,DNA 和组蛋白的核蛋白复合物——染色质,可以根据其构象作为转录的促进剂或障碍。染色质修饰酶通过建立特定的染色质组来调节 DNA 的可及性,这些染色质组对转录是有条件的或有抑制作用。在这篇综述中,我们将描述介导转录抑制的 H3K9/HP1 和 Polycomb 途径。我们讨论了这两种主要的表观遗传沉默模式是如何被动态调节的,以及它们如何促进胚胎发育的早期步骤。