Alteration of large-scale chromatin structure by estrogen receptor

Anne C. Nye, Ramji R. Rajendran, David L. Stenoien, Michael A. Mancini, Benita S. Katzenellenbogen, Andrew S. Belmont

Research output: Contribution to journalArticle

Abstract

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 ∼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.

Original languageEnglish (US)
Pages (from-to)3437-3449
Number of pages13
JournalMolecular and cellular biology
Volume22
Issue number10
DOIs
StatePublished - May 9 2002
Externally publishedYes

Fingerprint

Estrogen Receptors
Chromatin
Lac Repressors
Estradiol
Nuclear Receptor Coactivator 1
Ligands
Proteins
Viral Proteins
Cytoplasmic and Nuclear Receptors
Green Fluorescent Proteins
Histones
Transcriptional Activation
Chromosomes
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Alteration of large-scale chromatin structure by estrogen receptor. / Nye, Anne C.; Rajendran, Ramji R.; Stenoien, David L.; Mancini, Michael A.; Katzenellenbogen, Benita S.; Belmont, Andrew S.

In: Molecular and cellular biology, Vol. 22, No. 10, 09.05.2002, p. 3437-3449.

Research output: Contribution to journalArticle

Nye, Anne C. ; Rajendran, Ramji R. ; Stenoien, David L. ; Mancini, Michael A. ; Katzenellenbogen, Benita S. ; Belmont, Andrew S. / Alteration of large-scale chromatin structure by estrogen receptor. In: Molecular and cellular biology. 2002 ; Vol. 22, No. 10. pp. 3437-3449.
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