期刊
GENES & DEVELOPMENT
卷 33, 期 17-18, 页码 1159-1174出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.326348.119
关键词
chromatin; macrophages; nucleosome
资金
- European Research Council (ERC) [692789]
- EMBO long-term fellowship [1305-2015]
- Marie Curie Actions [LTFCOFUND2013/GA-2013-609409]
- Swiss National Science Foundation [P2EZP3_ 165206]
- Imperial College Research Fellowship
- European Research Council (ERC) [692789] Funding Source: European Research Council (ERC)
- Swiss National Science Foundation (SNF) [P2EZP3_165206] Funding Source: Swiss National Science Foundation (SNF)
Accessibility of the genomic regulatory information is largely controlled by the nucleosome-organizing activity of transcription factors (TFs). While stimulus-induced TFs bind to genomic regions that are maintained accessible by lineage-determining TFs, they also increase accessibility of thousands of cis-regulatory elements. Nucleosome remodeling events underlying such changes and their interplay with basal positioning are unknown. Here, we devised a novel quantitative framework discriminating different types of nucleosome remodeling events in micrococcal nuclease ChIP-seq (chromatin immunoprecipitation [ChIP] combined with high-throughput sequencing) data sets and used it to analyze nucleosome dynamics at stimulus-regulated cis-regulatory elements. At enhancers, remodeling preferentially affected poorly positioned nucleosomes while sparing well-positioned nucleosomes flanking the enhancer core, indicating that inducible TFs do not suffice to overrule basal nucleosomal organization maintained by lineage-determining TFs. Remodeling events appeared to be combinatorially driven by multiple TFs, with distinct TFs showing, however, different remodeling efficiencies. Overall, these data provide a systematic view of the impact of stimulation on nucleosome organization and genome accessibility in mammalian cells.
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