科學家繪製出人類增強子RNA基因座的高解析度圖譜
作者：
小柯機器人發布時間：2020/10/4 23:04:41
近日，美國德克薩斯大學MD安德森癌症中心Han Liang團隊繪製出人類增強子RNA基因座的高解析度圖譜，從而可表徵癌症中的超增強子活性。這一研究成果於2020年10月1日在線發表在國際學術期刊《癌細胞》上。
研究人員使用來自大型隊列的匯總RNA測序（RNA-seq）數據來表徵了超級增強子區域。超級增強子通常包含具有清晰增強子RNA（eRNA）表達峰的離散位點。研究人員在約377 Mb的超級增強子區域中發現了300000個eRNA基因座，這些區域受進化上保守的、定位良好的核小體調控，並且在癌症中經常失調。
通過解析具有增強細胞類型特異性的腫瘤內異質性，eRNA為癌症表型提供了超越mRNA表達所提供的解釋能力。這項研究提供了eRNA基因座的高解析度圖譜，從而可以通過RNA-seq和用戶友好的數據門戶網站量化超級增強子的活性，來進行廣泛的生物醫學研究。
據介紹，儘管增強子在癌症中起著關鍵作用，但量化臨床樣品中的增強子活性仍然具有挑戰性，尤其是對於超級增強子。增強子活性可以從eRNA信號推斷出來，這需要增強子轉錄基因座的定義。只有一小部分人類eRNA基因座被精確鑑定，從而限制了對增強子介導致癌機制的研究。
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