小柯机器人

系统鉴定人细胞中的沉默子
2020-02-26 14:49

美国斯坦福大学Michael P. Snyder小组在新研究中,系统鉴定了人细胞中的沉默子。该研究成果于2020年2月24日在线发表在《自然—遗传学》上。

研究人员开发了一种系统,该系统基于沉默子介导的caspase 9转录抑制,在全基因组上识别沉默子区域。研究人员发现沉默子分布广泛,并且可能以组织特异性的方式起作用。这些沉默子具有独特的表观遗传学特征,并与特定的转录因子相关。

沉默子还以染色体结构域和远距离相互作用的方式作用于多个基因。与药物转运蛋白基因ABCC2和ABCG2相关的沉默子区域缺失会引起化学耐药性。

总的来说,该研究表明组织特异性沉默在整个人类基因组中广泛分布,并且可能对基因表达和人类生物学的调控做出了重要贡献。

据了解,人类基因组中大部分基因都不编码蛋白质。这些非编码区中许多都包含调控基因表达的重要调控序列。迄今为止,大多数研究都集中在增强子等激活剂上,但是尚未系统研究抑制基因表达的区域-沉默子。

附:英文原文

Title: Systematic identification of silencers in human cells

Author: Baoxu Pang, Michael P. Snyder

Issue&Volume: 2020-02-24

Abstract: The majority of the human genome does not encode proteins. Many of these noncoding regions contain important regulatory sequences that control gene expression. To date, most studies have focused on activators such as enhancers, but regions that repress gene expression—silencers—have not been systematically studied. We have developed a system that identifies silencer regions in a genome-wide fashion on the basis of silencer-mediated transcriptional repression of caspase9. We found that silencers are widely distributed and may function in a tissue-specific fashion. These silencers harbor unique epigenetic signatures and are associated with specific transcription factors. Silencers also act at multiple genes, and at the level of chromosomal domains and long-range interactions. Deletion of silencer regions linked to the drug transporter genes ABCC2 and ABCG2 caused chemo-resistance. Overall, our study demonstrates that tissue-specific silencing is widespread throughout the human genome and probably contributes substantially to the regulation of gene expression and human biology.

DOI: 10.1038/s41588-020-0578-5

Source: https://www.nature.com/articles/s41588-020-0578-5

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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