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高度互连的增强子群体调控人类间充质干细胞中的谱系决定基因
2020-10-10 13:52

南丹麦大学Susanne Mandrup研究团队发现,高度互连的增强子群体调控人类间充质干细胞中的谱系决定基因。这一研究成果于2020年10月5日在线发表在国际学术期刊《自然—遗传学》上。

研究人员使用高通量染色体构象增强子捕获来研究了人类间充质干细胞分化过程中的增强子-增强子相互作用。研究人员发现增强子形成了一个精细的网络,其在分化过程中是动态的,并与增强子活性的变化相耦合。诱饵增强子上的转录因子(TF)放大了靶增强子上的TF结合,这种现象被称为TF互作的稳定。此外,高度互连的增强子(HICE)充当整合中心,通过形成三维增强子群体来协调分化,其中,HICE和其他增强子在表型上重要的基因启动子上汇合。
 
总的来说,这些结果表明,增强子相互作用在增强子功能的调节中起着关键作用,而HICE对于信号整合和基因组区室化都是重要的。
 
据介绍,脂肪细胞的分化是由转录调节因子波动引起的,从而重编程增强子格局并改变启动子相互作用组的连接。
 
附:英文原文

Title: Highly interconnected enhancer communities control lineage-determining genes in human mesenchymal stem cells

Author: Jesper G. S. Madsen, Maria S. Madsen, Alexander Rauch, Sofie Traynor, Elvira L. Van Hauwaert, Anders K. Haakonsson, Biola M. Javierre, Mette Hyldahl, Peter Fraser, Susanne Mandrup

Issue&Volume: 2020-10-05

Abstract: Adipocyte differentiation is driven by waves of transcriptional regulators that reprogram the enhancer landscape and change the wiring of the promoter interactome. Here, we use high-throughput chromosome conformation enhancer capture to interrogate the role of enhancer-to-enhancer interactions during differentiation of human mesenchymal stem cells. We find that enhancers form an elaborate network that is dynamic during differentiation and coupled with changes in enhancer activity. Transcription factors (TFs) at baited enhancers amplify TF binding at target enhancers, a phenomenon we term cross-interaction stabilization of TFs. Moreover, highly interconnected enhancers (HICE) act as integration hubs orchestrating differentiation by the formation of three-dimensional enhancer communities, inside which, HICE, and other enhancers, converge on phenotypically important gene promoters. Collectively, these results indicate that enhancer interactions play a key role in the regulation of enhancer function, and that HICE are important for both signal integration and compartmentalization of the genome. High-throughput chromosome conformation enhancer capture identifies dynamic enhancer networks that regulate differentiation of human mesenchymal stem cells. Transcription factors (TFs) at baited enhancers appear to stabilize TF binding at target enhancers.

DOI: 10.1038/s41588-020-0709-z

Source: https://www.nature.com/articles/s41588-020-0709-z

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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