Activation of estrogen receptor-alpha by E2 or EGF induces temporally distinct patterns of large-scale chromatin modification and mRNA transcription

PLoS One. 2008 May 28;3(5):e2286. doi: 10.1371/journal.pone.0002286.


Estrogen receptor-alpha (ER) transcription function is regulated in a ligand-dependent (e.g., estradiol, E2) or ligand-independent (e.g., growth factors) manner. Our laboratory seeks to understand these two modes of action. Using a cell line that contains a visible prolactin enhancer/promoter array (PRL-HeLa) regulated by ER, we analyzed ER response to E2 and EGF by quantifying image-based results. Data show differential recruitment of GFP-ER to the array, with the AF1 domain playing a vital role in EGF-mediated responsiveness. Temporal analyses of large-scale chromatin dynamics, and accumulation of array-localized reporter mRNA over 24 hours showed that the EGF response consists of a single pulse of reporter mRNA accumulation concomitant with transient increase in array decondensation. Estradiol induced a novel cyclical pattern of mRNA accumulation with a sustained increase in array decondensation. Collectively, our work shows that there is a stimuli-specific pattern of large-scale chromatin modification and transcript levels by ER.

Publication types

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

MeSH terms

  • Chromatin / metabolism*
  • Epidermal Growth Factor / pharmacology*
  • Estradiol / pharmacology*
  • Estrogen Receptor alpha / metabolism*
  • HeLa Cells
  • Humans
  • In Situ Hybridization, Fluorescence
  • RNA, Messenger / genetics*
  • Transcription, Genetic*


  • Chromatin
  • Estrogen Receptor alpha
  • RNA, Messenger
  • Estradiol
  • Epidermal Growth Factor