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

Academic Article

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. © 2013 Elsevier Inc.
  • Published In

  • Molecular Cell  Journal
  • Digital Object Identifier (doi)

    Author List

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

  • 25
  • End Page

  • 36
  • Volume

  • 52
  • Issue

  • 1