Modeling cis-regulation with a compendium of genome-wide histone H3K27ac profiles.
Modeling cis-regulation with a compendium of genome-wide histone H3K27ac profiles.
复制标题
DOI：
10.1101/gr.201574.115
复制
发表时间：
2016-10
期刊：
影响因子：
7
通讯作者：
Liu XS
中科院分区：
文献类型：
--
作者：
Wang S;Zang C;Xiao T;Fan J;Mei S;Qin Q;Wu Q;Li X;Xu K;He HH;Brown M;Meyer CA;Liu XS
基于模型的基因表达调控分析（MARGE）是一个框架，用于解释H3 K27 ac染色质环境和差异表达基因集之间的关系。该框架有三个主要功能：MARGE-potential，MARGE-express和MARGE-cistrome。MARGE电位将每个基因的调节电位（RP）定义为通过距转录起始位点的基因组距离的函数加权的H3 K27 ac ChIP-seq信号的总和。MARGE框架包括来自365个人类和267个小鼠H3 K27 ac ChIP-seq数据集的RP纲要。相对RP，缩放使用此纲要，是上级的预测BET（溴结构域和末端外结构域）抑制剂抑制基因的超级增强剂。MARGE-express使用逻辑回归从纲要中检索相关的H3 K27 ac谱，以准确地模拟差异表达基因的查询集，在MSigDB的671个不同基因集上进行了测试。MARGE-cistrome采用一种新的半监督学习方法来识别调控基因集的顺式调控元件。MARGE-cistrome利用来自H3 K27 ac信号的信息，该信号位于从已发表的人类和小鼠DNase-seq数据中鉴定的DNase I超敏位点。我们在前列腺癌细胞系LNCaP-abl中对多个转录和表观遗传调节因子进行siRNA沉默后，在新生成的RNA-seq和H3 K27 ac ChIP-seq谱上测试了框架。MARGE-cistrome可以在没有匹配的H3 K27 ac ChIP-seq数据的情况下预测沉默的转录因子的结合位点。即使匹配的H3 K27 ac ChIP-seq配置文件可用，MARGE也会利用公共H3 K27 ac配置文件来增强这些数据。这项研究表明，整合大量的历史表观遗传学数据的转录调控基因组研究的优势。
Model-based analysis of regulation of gene expression (MARGE) is a framework for interpreting the relationship between the H3K27ac chromatin environment and differentially expressed gene sets. The framework has three main functions: MARGE-potential, MARGE-express, and MARGE-cistrome. MARGE-potential defines a regulatory potential (RP) for each gene as the sum of H3K27ac ChIP-seq signals weighted by a function of genomic distance from the transcription start site. The MARGE framework includes a compendium of RPs derived from 365 human and 267 mouse H3K27ac ChIP-seq data sets. Relative RPs, scaled using this compendium, are superior to superenhancers in predicting BET (bromodomain and extraterminal domain) -inhibitor repressed genes. MARGE-express, which uses logistic regression to retrieve relevant H3K27ac profiles from the compendium to accurately model a query set of differentially expressed genes, was tested on 671 diverse gene sets from MSigDB. MARGE-cistrome adopts a novel semisupervised learning approach to identify cis-regulatory elements regulating a gene set. MARGE-cistrome exploits information from H3K27ac signal at DNase I hypersensitive sites identified from published human and mouse DNase-seq data. We tested the framework on newly generated RNA-seq and H3K27ac ChIP-seq profiles upon siRNA silencing of multiple transcriptional and epigenetic regulators in a prostate cancer cell line, LNCaP-abl. MARGE-cistrome can predict the binding sites of silenced transcription factors without matched H3K27ac ChIP-seq data. Even when the matching H3K27ac ChIP-seq profiles are available, MARGE leverages public H3K27ac profiles to enhance these data. This study demonstrates the advantage of integrating a large compendium of historical epigenetic data for genomic studies of transcriptional regulation.
登录
查看更多内容
影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
46.9
作者：
Ernst J;Kellis M
通讯作者：
Kellis M
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
4
作者：
Declercq, Jeroen;Sheshadri, Preethi;Kumar, Anujith
通讯作者：
Kumar, Anujith