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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Gertz, J; Savic, D; Varley, KE; Partridge, EC; Safi, A; Jain, P; Cooper, GM; Reddy, TE; Crawford, GE; Myers, RM

Published Date

  • October 2013

Published In

Volume / Issue

  • 52 / 1

Start / End Page

  • 25 - 36

PubMed ID

  • 24076218

Pubmed Central ID

  • 24076218

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

International Standard Serial Number (ISSN)

  • 1097-2765

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2013.08.037

Language

  • eng