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科学家绘制出人类增强子RNA基因座的高分辨率图谱
2020-10-04 23:04

近日,美国德克萨斯大学MD安德森癌症中心Han Liang团队绘制出人类增强子RNA基因座的高分辨率图谱,从而可表征癌症中的超增强子活性。这一研究成果于2020年10月1日在线发表在国际学术期刊《癌细胞》上。

研究人员使用来自大型队列的汇总RNA测序(RNA-seq)数据来表征了超级增强子区域。超级增强子通常包含具有清晰增强子RNA(eRNA)表达峰的离散位点。研究人员在约377 Mb的超级增强子区域中发现了300000个eRNA基因座,这些区域受进化上保守的、定位良好的核小体调控,并且在癌症中经常失调。
 
通过解析具有增强细胞类型特异性的肿瘤内异质性,eRNA为癌症表型提供了超越mRNA表达所提供的解释能力。这项研究提供了eRNA基因座的高分辨率图谱,从而可以通过RNA-seq和用户友好的数据门户网站量化超级增强子的活性,来进行广泛的生物医学研究。
 
据介绍,尽管增强子在癌症中起着关键作用,但量化临床样品中的增强子活性仍然具有挑战性,尤其是对于超级增强子。增强子活性可以从eRNA信号推断出来,这需要增强子转录基因座的定义。只有一小部分人类eRNA基因座被精确鉴定,从而限制了对增强子介导致癌机制的研究。
 
附:英文原文

Title: A High-Resolution Map of Human Enhancer RNA Loci Characterizes Super-enhancer Activities in Cancer

Author: Han Chen, Han Liang

Issue&Volume: 2020-10-1

Abstract: Although enhancers play critical roles in cancer, quantifying enhancer activitiesin clinical samples remains challenging, especially for super-enhancers. Enhanceractivities can be inferred from enhancer RNA (eRNA) signals, which requires enhancertranscription loci definition. Only a small proportion of human eRNA loci has beenprecisely identified, limiting investigations of enhancer-mediated oncogenic mechanisms.Here, we characterize super-enhancer regions using aggregated RNA sequencing (RNA-seq)data from large cohorts. Super-enhancers usually contain discrete loci featuring sharpeRNA expression peaks. We identify >300,000 eRNA loci in ~377 Mb super-enhancer regionsthat are regulated by evolutionarily conserved, well-positioned nucleosomes and arefrequently dysregulated in cancer. The eRNAs provide explanatory power for cancerphenotypes beyond that provided by mRNA expression through resolving intratumoralheterogeneity with enhancer cell-type specificity. Our study provides a high-resolutionmap of eRNA loci through which super-enhancer activities can be quantified by RNA-seqand a user-friendly data portal, enabling a broad range of biomedical investigations.

DOI: 10.1016/j.ccell.2020.08.020

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30431-1

Cancer Cell:《癌细胞》,创刊于2002年。隶属于细胞出版社,最新IF:38.585
官方网址:https://www.cell.com/cancer-cell/home
投稿链接:https://www.editorialmanager.com/cancer-cell/default.aspx


本期文章:《癌细胞》:Online/在线发表

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