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

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

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Line
  • Conserved Sequence
  • DNA Methylation
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / drug effects
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism*
  • Estrogens / pharmacology
  • Evolution, Molecular
  • Gene Expression Regulation
  • Humans
  • Mice
  • Models, Biological
  • Promoter Regions, Genetic* / drug effects
  • RNA Interference
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism
  • Response Elements
  • Thermodynamics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection

Substances

  • Estrogen Receptor alpha
  • Estrogens
  • Receptors, Glucocorticoid
  • Transcription Factors
  • estrogen receptor alpha, human
  • Estradiol

Associated data

  • GEO/GSE32465
  • GEO/GSE32970
  • GEO/GSE38234
  • GEO/GSE49993