Alteration of large-scale chromatin structure by estrogen receptor

Mol Cell Biol. 2002 May;22(10):3437-49. doi: 10.1128/MCB.22.10.3437-3449.2002.


The estrogen receptor (ER), a member of the nuclear hormone receptor superfamily important in human physiology and disease, recruits coactivators which modify local chromatin structure. Here we describe effects of ER on large-scale chromatin structure as visualized in live cells. We targeted ER to gene-amplified chromosome arms containing large numbers of lac operator sites either directly, through a lac repressor-ER fusion protein (lac rep-ER), or indirectly, by fusing lac repressor with the ER interaction domain of the coactivator steroid receptor coactivator 1. Significant decondensation of large-scale chromatin structure, comparable to that produced by the approximately 150-fold-stronger viral protein 16 (VP16) transcriptional activator, was produced by ER in the absence of estradiol using both approaches. Addition of estradiol induced a partial reversal of this unfolding by green fluorescent protein-lac rep-ER but not by wild-type ER recruited by a lac repressor-SRC570-780 fusion protein. The chromatin decondensation activity did not require transcriptional activation by ER nor did it require ligand-induced coactivator interactions, and unfolding did not correlate with histone hyperacetylation. Ligand-induced coactivator interactions with helix 12 of ER were necessary for the partial refolding of chromatin in response to estradiol using the lac rep-ER tethering system. This work demonstrates that when tethered or recruited to DNA, ER possesses a novel large-scale chromatin unfolding activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylation
  • Animals
  • CHO Cells
  • Cell Cycle Proteins*
  • Chromatin / chemistry
  • Chromatin / metabolism*
  • Cricetinae
  • Drosophila Proteins
  • Estradiol / metabolism
  • Estrogen Receptor Modulators / metabolism
  • Estrogen Receptor alpha
  • Genes, Reporter
  • Green Fluorescent Proteins
  • Histone Acetyltransferases
  • Histones / metabolism
  • Humans
  • Indicators and Reagents / metabolism
  • Lac Operon / genetics*
  • Ligands
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Nuclear Receptor Coactivator 1
  • Nucleic Acid Conformation
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Cell Cycle Proteins
  • Chromatin
  • Drosophila Proteins
  • Estrogen Receptor Modulators
  • Estrogen Receptor alpha
  • Histones
  • Indicators and Reagents
  • Ligands
  • Luminescent Proteins
  • Receptors, Estrogen
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Transcription Factors
  • brm protein, Drosophila
  • Green Fluorescent Proteins
  • Estradiol
  • Histone Acetyltransferases
  • NCOA1 protein, human
  • Nuclear Receptor Coactivator 1