期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：6
页码：E645-E654
DOI：10.1073/pnas.1312523111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：A problem of substantial interest is to systematically map variation in chromatin structure to gene-expression regulation across conditions, environments, or differentiated cell types. We developed and applied a quantitative framework for determining the existence, strength, and type of relationship between high-resolution chromatin structure in terms of DNaseI hypersensitivity and genome-wide gene-expression levels in 20 diverse human cell types. We show that [~]25% of genes show cell-type-specific expression explained by alterations in chromatin structure. We find that distal regions of chromatin structure (e.g., {+/-}200 kb) capture more genes with this relationship than local regions (e.g., {+/-}2.5 kb), yet the local regions show a more pronounced effect. By exploiting variation across cell types, we were capable of pinpointing the most likely hypersensitive sites related to cell-type-specific expression, which we show have a range of contextual uses. This quantitative framework is likely applicable to other settings aimed at relating continuous genomic measurements to gene-expression variation.
