A High-Resolution Map of Human Enhancer RNA Loci Characterizes Super-enhancer Activities in Cancer.
A High-Resolution Map of Human Enhancer RNA Loci Characterizes Super-enhancer Activities in Cancer.
复制标题
DOI：
10.1016/j.ccell.2020.08.020
复制
发表时间：
2020-11-09
期刊：
影响因子：
50.3
通讯作者：
Liang H
中科院分区：
文献类型：
--
作者：
Chen H;Liang H
尽管增强子在癌症中起着关键作用，但定量临床样品中的增强子活性仍然具有挑战性，特别是对于超级增强子。增强子活性可以从增强子RNA（eRNA）信号推断，这需要增强子转录位点的定义。只有一小部分的人类eRNA基因座已被精确地确定，限制了增强子介导的致癌机制的调查。在这里，我们使用来自大型队列的聚合RNA-seq数据来表征超级增强子区域。超级增强子通常含有以尖锐eRNA表达峰为特征的离散基因座。我们在~377 Mb的超级增强子区域中鉴定了> 300，000个eRNA基因座，这些基因座由进化上保守的、位置良好的核小体调节，并且在癌症中经常失调。eRNA通过增强子细胞类型特异性解决肿瘤内异质性，提供了对癌症表型的解释能力，超出了mRNA表达所提供的解释能力。我们的研究提供了一个高分辨率的eRNA基因座图谱，通过该图谱，可以通过RNA-seq和用户友好的数据门户来量化超级增强子的活性，从而实现广泛的生物医学研究。Chen和Liang提供了eRNA基因座的高分辨率图谱，通过该图谱可以方便地通过RNA-seq定量超级增强子活性。癌症样品中的eRNA信号具有临床相关性，并且通过用增强子细胞类型特异性解决肿瘤内异质性，为癌症表型提供了超出mRNA所提供的解释力。
Although enhancers play critical roles in cancer, quantifying enhancer activities in clinical samples remains challenging, especially for super-enhancers. Enhancer activities can be inferred from enhancer RNA (eRNA) signals, which requires enhancer transcription loci definition. Only a small proportion of human eRNA loci has been precisely identified, limiting investigations of enhancer-mediated oncogenic mechanisms. Here we characterize super-enhancer regions using aggregated RNA-seq data from large cohorts. Super-enhancers usually contain discrete loci featuring sharp eRNA expression peaks. We identify >300,000 eRNA loci in ~377 Mb super-enhancer regions that are regulated by evolutionarily conserved, well-positioned nucleosomes and are frequently dysregulated in cancer. The eRNAs provide explanatory power for cancer phenotypes beyond that provided by mRNA expression through resolving intratumoral heterogeneity with enhancer cell-type specificity. Our study provides a high-resolution map of eRNA loci through which super-enhancer activities can be quantified by RNA-seq and a user-friendly data portal, enabling a broad range of biomedical investigations. Chen and Liang provide a high-resolution map of eRNA loci through which super-enhancer activities can be conveniently quantified by RNA-seq. The eRNA signals in cancer samples are clinically relevant and provide additional explanatory power for cancer phenotypes beyond those provided by mRNAs through resolving intra-tumor heterogeneity with enhancer cell-type specificity.
登录
查看更多内容
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
影响因子：
10.5
作者：
Catarino RR;Stark A
通讯作者：
Stark A
模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS
影响因子：
12.4
作者：
Du Y;Liu Z;Cao X;Chen X;Chen Z;Zhang X;Zhang X;Jiang C
通讯作者：
Jiang C