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孤儿CpG岛放大稳定的增强子调节活性并确定靶基因反应性
作者:小柯机器人 发布时间:2021/6/30 23:40:44

2021年6月28日,《自然—遗传学》杂志在线发表了德国科学家的一项最新成果。来自科隆大学的Alvaro Rada-Iglesias小组发现,孤儿CpG岛放大稳定的增强子调节活性并确定靶基因反应性。

研究人员表示,CpG岛(CGI)是脊椎动物基因组的一个普遍特征,与约70%的基因启动子相关。CGI通过赋予附近的启动子独特的染色质特性来控制转录起始。此外,还有数以千计的远端或孤儿CGI(oCGI),其功能相关性几乎不为人所知。

研究人员表明oCGI是稳定增强子的重要组成部分,可增强其远程调节活动并控制其靶基因的反应性。在小鼠胚胎干细胞中使用敲入策略,研究人员在包含具有不同类型启动子的基因的拓扑关联域中引入了带有或不带有oCGI的稳定增强子。

对所得细胞系的分析表明,oCGI充当系留元件,促进稳定的增强子和位于远端的基因之间的物理和功能交流,特别是那些在其启动子中具有大CGI簇的基因。因此,通过充当基因-增强子相容性的遗传决定因素,CGI 可以在生理和潜在病理条件下促进基因表达控制。

附:英文原文

Title: Orphan CpG islands amplify poised enhancer regulatory activity and determine target gene responsiveness

Author: Tomas Pachano, Vctor Snchez-Gaya, Thais Ealo, Maria Mariner-Faul, Tore Bleckwehl, Helena G. Asenjo, Patricia Respuela, Sara Cruz-Molina, Mara Muoz-San Martn, Endika Haro, Wilfred F. J. van IJcken, David Landeira, Alvaro Rada-Iglesias

Issue&Volume: 2021-06-28

Abstract: CpG islands (CGIs) represent a widespread feature of vertebrate genomes, being associated with ~70% of all gene promoters. CGIs control transcription initiation by conferring nearby promoters with unique chromatin properties. In addition, there are thousands of distal or orphan CGIs (oCGIs) whose functional relevance is barely known. Here we show that oCGIs are an essential component of poised enhancers that augment their long-range regulatory activity and control the responsiveness of their target genes. Using a knock-in strategy in mouse embryonic stem cells, we introduced poised enhancers with or without oCGIs within topologically associating domains harboring genes with different types of promoters. Analysis of the resulting cell lines revealed that oCGIs act as tethering elements that promote the physical and functional communication between poised enhancers and distally located genes, particularly those with large CGI clusters in their promoters. Therefore, by acting as genetic determinants of gene–enhancer compatibility, CGIs can contribute to gene expression control under both physiological and potentially pathological conditions.

DOI: 10.1038/s41588-021-00888-x

Source: https://www.nature.com/articles/s41588-021-00888-x

期刊信息

Nature Methods:《自然—方法学》,创刊于2004年。隶属于施普林格·自然出版集团,最新IF:28.467
官方网址:https://www.nature.com/nmeth/
投稿链接:https://mts-nmeth.nature.com/cgi-bin/main.plex