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。
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