Activation of estrogen receptor-alpha by E2 or EGF induces temporally distinct patterns of large-scale chromatin modification and mRNA transcription.
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.
Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America. valeria.bernoembl.it
Valeria
V
Berno
Larbi
L
Amazit
Cruz
C
Hinojos
Jeannie
J
Zhong
Maureen G
MG
Mancini
Zelton Dave
ZD
Sharp
Michael A
MA
Mancini
D002843:Chromatin / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D012333:RNA, Messenger / Q000235:genetics*; D014158:Transcription, Genetic
D002843:Chromatin; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D004958:Estradiol; D004815:Epidermal Growth Factor