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Mol Cell. 2013 Oct 10;52(1):25-36. doi: 10.1016/j.molcel.2013.08.037. Epub 2013 Sep 26.

Distinct properties of cell-type-specific and shared transcription factor binding sites.

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1
HudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806, USA.

Abstract

Most human transcription factors bind a small subset of potential genomic sites and often use different subsets in different cell types. To identify mechanisms that govern cell-type-specific transcription factor binding, we used an integrative approach to study estrogen receptor α (ER). We found that ER exhibits two distinct modes of binding. Shared sites, bound in multiple cell types, are characterized by high-affinity estrogen response elements (EREs), inaccessible chromatin, and a lack of DNA methylation, while cell-specific sites are characterized by a lack of EREs, co-occurrence with other transcription factors, and cell-type-specific chromatin accessibility and DNA methylation. These observations enabled accurate quantitative models of ER binding that suggest tethering of ER to one-third of cell-specific sites. The distinct properties of cell-specific binding were also observed with glucocorticoid receptor and for ER in primary mouse tissues, representing an elegant genomic encoding scheme for generating cell-type-specific gene regulation.

PMID:
24076218
PMCID:
PMC3811135
DOI:
10.1016/j.molcel.2013.08.037
[Indexed for MEDLINE]
Free PMC Article
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