研究揭示沉默子在小鼠发育中的功能
2020-02-26   阅读:320   来源:自然

美国杰克逊基因组医学实验室Chia-Lin Wei研究组,利用染色质相互作用分析阐述了与PRC2结合的沉默子在小鼠发育中的作用。该项研究成果在线发表在2020年2月24日的《自然—遗传学》上。

研究人员对多梳蛋白抑制复合体2(PRC2)的染色质相互作用进行了分析以揭示沉默子、它们的分子特征和相关的染色质连接性。PRC2是转录基因沉默的关键诱导物。顺式调控沉默子的系统分析揭示了它们的染色质特征和靶向基因的特异性。

小鼠中某些与PRC2结合的沉默子缺失会导致其相互作用和多效性发育表型基因的转录降低,造成胚胎致死。尽管某些PRC2结合元件在多能细胞中充当沉默子,但它们在发育过程中可以转变为活性组织特异性的增强子,从而突出了其调节功能的多样性。

该研究揭示了沉默子及其相关染色质结构的分子特征,并提出了表观遗传沉默基因靶向再激活的可能性。

研究人员表示,在动物发育过程中,转录激活与抑制之间的平衡调控了谱系特异性基因的表达。以增强子为中心的转录激活机制已取得重要进展,但是对沉默子在正常发育中的作用仍知之甚少。

附:英文原文

Title: Chromatin interaction analyses elucidate the roles of PRC2-bound silencers in mouse development

Author: Chew Yee Ngan, Chee Hong Wong, Harianto Tjong, Wenbo Wang, Rachel L. Goldfeder, Cindy Choi, Hao He, Liang Gong, Junyan Lin, Barbara Urban, Julianna Chow, Meihong Li, Joanne Lim, Vivek Philip, Stephen A. Murray, Haoyi Wang, Chia-Lin Wei

Issue&Volume: 2020-02-24

Abstract: Lineage-specific gene expression is modulated by a balance between transcriptional activation and repression during animal development. Knowledge about enhancer-centered transcriptional activation has advanced considerably, but silencers and their roles in normal development remain poorly understood. Here, we performed chromatin interaction analyses of Polycomb repressive complex2 (PRC2), a key inducer of transcriptional gene silencing, to uncover silencers, their molecular identity and associated chromatin connectivity. Systematic analysis of cis-regulatory silencer elements reveals their chromatin features and gene-targeting specificity. Deletion of certain PRC2-bound silencers in mice results in transcriptional derepression of their interacting genes and pleiotropic developmental phenotypes, including embryonic lethality. While some PRC2-bound elements function as silencers in pluripotent cells, they can transition into active tissue-specific enhancers during development, highlighting their regulatory versatility. Our study characterizes the molecular profile of silencers and their associated chromatin architectures, and suggests the possibility of targeted reactivation of epigenetically silenced genes.

DOI: 10.1038/s41588-020-0581-x

编辑:小柯机器人

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