PLoS ONE (May 2008)

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

  • Valeria Berno,
  • Larbi Amazit,
  • Cruz Hinojos,
  • Jeannie Zhong,
  • Maureen G Mancini,
  • Zelton Dave Sharp,
  • Michael A Mancini

DOI
https://doi.org/10.1371/journal.pone.0002286
Journal volume & issue
Vol. 3, no. 5
p. e2286

Abstract

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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.