绘制和分析九种人类细胞类型中的染色质状态动态。

Mapping and analysis of chromatin state dynamics in nine human cell types.

机构信息

Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.

出版信息

Nature. 2011 May 5;473(7345):43-9. doi: 10.1038/nature09906. Epub 2011 Mar 23.

Abstract

Chromatin profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. The approach is especially well suited to the characterization of non-coding portions of the genome, which critically contribute to cellular phenotypes yet remain largely uncharted. Here we map nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions. Focusing on cell-type-specific patterns of promoters and enhancers, we define multicell activity profiles for chromatin state, gene expression, regulatory motif enrichment and regulator expression. We use correlations between these profiles to link enhancers to putative target genes, and predict the cell-type-specific activators and repressors that modulate them. The resulting annotations and regulatory predictions have implications for the interpretation of genome-wide association studies. Top-scoring disease single nucleotide polymorphisms are frequently positioned within enhancer elements specifically active in relevant cell types, and in some cases affect a motif instance for a predicted regulator, thus suggesting a mechanism for the association. Our study presents a general framework for deciphering cis-regulatory connections and their roles in disease.

摘要

染色质谱分析已成为基因组注释和检测调控活性的有力手段。这种方法特别适合于对基因组中非编码部分的特征描述,这些非编码部分对细胞表型有重要贡献,但在很大程度上仍未被探索。在这里,我们在九种细胞类型中绘制了九个染色质标记,以系统地描述调控元件、它们的细胞类型特异性以及它们的功能相互作用。我们专注于启动子和增强子的细胞类型特异性模式,为染色质状态、基因表达、调控基序富集和调节因子表达定义了多细胞活性谱。我们使用这些谱之间的相关性将增强子与假定的靶基因联系起来,并预测调节它们的细胞类型特异性激活子和抑制剂。由此产生的注释和调控预测对全基因组关联研究的解释具有重要意义。排名靠前的疾病单核苷酸多态性经常位于在相关细胞类型中特异性活跃的增强子元件内,并且在某些情况下影响预测调节剂的一个基序实例,从而为关联提供了一种机制。我们的研究提出了一个解析顺式调控连接及其在疾病中的作用的一般框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d44/3088773/1c828101aa8f/nihms-270546-f0001.jpg

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