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Region Capture Micro-C揭示增强子和启动子凝聚成的嵌套微区
作者:小柯机器人 发布时间:2023/5/16 15:08:53

美国麻省理工学院Anders S. Hansen团队利用Region Capture Micro-C揭示增强子和启动子凝聚成的嵌套微区。相关论文于2023年5月8日发表在《自然—遗传学》杂志上。

研究人员表示,尽管增强子是哺乳动物基因表达的核心调节因子,但增强子-促进子(E-P)相互作用的机制仍不清楚。染色体构象捕获(3C)方法能有效地捕获大规模的三维(3D)基因组结构,但却难以达到解决细小的E-P相互作用所需的深度。

通过将基于微球菌核酸酶(MNase)的3C与平铺式区域捕获方法相结合,研究人员开发了区域捕获Micro-C(RCMC),并产生了最深的三维基因组图谱,这只需适度的测序。通过在小鼠胚胎干细胞中应用RCMC并达到相当于约3170亿个独特的接触,RCMC揭示了以前无法解决的高度嵌套和集中的三维互动模式,研究人员称之为微区。微区经常连接增强子和启动子,尽管环状挤压的丧失和转录的抑制破坏了一些微区,但大多数微区基本上不受影响。因此,研究人员提出许多E-P相互作用是通过区室化机制形成的,这可能部分地解释了为什么急性粘连蛋白的耗竭只适度地影响了全局基因表达。

附:英文原文

Title: Region Capture Micro-C reveals coalescence of enhancers and promoters into nested microcompartments

Author: Goel, Viraat Y., Huseyin, Miles K., Hansen, Anders S.

Issue&Volume: 2023-05-08

Abstract: Although enhancers are central regulators of mammalian gene expression, the mechanisms underlying enhancer–promoter (E-P) interactions remain unclear. Chromosome conformation capture (3C) methods effectively capture large-scale three-dimensional (3D) genome structure but struggle to achieve the depth necessary to resolve fine-scale E-P interactions. Here, we develop Region Capture Micro-C (RCMC) by combining micrococcal nuclease (MNase)-based 3C with a tiling region-capture approach and generate the deepest 3D genome maps reported with only modest sequencing. By applying RCMC in mouse embryonic stem cells and reaching the genome-wide equivalent of ~317 billion unique contacts, RCMC reveals previously unresolvable patterns of highly nested and focal 3D interactions, which we term microcompartments. Microcompartments frequently connect enhancers and promoters, and although loss of loop extrusion and inhibition of transcription disrupts some microcompartments, most are largely unaffected. We therefore propose that many E-P interactions form through a compartmentalization mechanism, which may partially explain why acute cohesin depletion only modestly affects global gene expression.

DOI: 10.1038/s41588-023-01391-1

Source: https://www.nature.com/articles/s41588-023-01391-1

期刊信息

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