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新研究在碱基对分辨率上定义基因组结构
2021-06-13 15:05

英国牛津大学James O. J. Davies小组在碱基对分辨率上定义基因组结构。相关论文发于2021年6月9日在线发表在《自然》杂志上。

研究人员表示,在高等真核生物中,许多基因受与启动子相距104-106个碱基对(bp)的增强子调控。增强子包含转录因子结合位点(通常约为7-22 bp),并且启动子和增强子之间的物理接触被认为是调节基因表达所必需的。尽管染色质结构已经以1千碱基及以上的分辨率被广泛绘制;在决定基因表达的蛋白质的规模上定义物理接触是不可能的。

研究人员使用染色体构象捕获方法(Micro-Capture-C)详细定义了这些相互作用,该方法能够以碱基对分辨率确定不同类别的调控元件之间的物理接触。研究人员发现增强子、启动子和CCCTC结合因子(CTCF)位点之间存在高度点状的接触,并表明转录因子在维持增强子和启动子之间的接触中具有重要作用。数据显示,当活性启动子和增强子位于介入染色质内时,CTCF位点之间的相互作用会增加。这些数据支持了一种模型:染色质环挤压依赖于活性启动子和增强子上的粘连蛋白加载,这解释了组织特异性染色质域的形成,而却CTCF结合没有变化。 

附:英文原文

Title: Defining genome architecture at base-pair resolution

Author: Peng Hua, Mohsin Badat, Lars L. P. Hanssen, Lance D. Hentges, Nicholas Crump, Damien J. Downes, Danuta M. Jeziorska, A. Marieke Oudelaar, Ron Schwessinger, Stephen Taylor, Thomas A. Milne, Jim R. Hughes, Doug R. Higgs, James O. J. Davies

Issue&Volume: 2021-06-09

Abstract: In higher eukaryotes, many genes are regulated by enhancers that are 104–106 base pairs (bp) away from the promoter. Enhancers contain transcription-factor-binding sites (which are typically around 7–22 bp), and physical contact between the promoters and enhancers is thought to be required to modulate gene expression. Although chromatin architecture has been mapped extensively at resolutions of 1 kilobase and above; it has not been possible to define physical contacts at the scale of the proteins that determine gene expression. Here we define these interactions in detail using a chromosome conformation capture method (Micro-Capture-C) that enables the physical contacts between different classes of regulatory elements to be determined at base-pair resolution. We find that highly punctate contacts occur between enhancers, promoters and CCCTC-binding factor (CTCF) sites and we show that transcription factors have an important role in the maintenance of the contacts between enhancers and promoters. Our data show that interactions between CTCF sites are increased when active promoters and enhancers are located within the intervening chromatin. This supports a model in which chromatin loop extrusion1 is dependent on cohesin loading at active promoters and enhancers, which explains the formation of tissue-specific chromatin domains without changes in CTCF binding.

DOI: 10.1038/s41586-021-03639-4

Source: https://www.nature.com/articles/s41586-021-03639-4

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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