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PMID: 20181721 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Global characterization of transcriptional impact of the SRC-3 coregulator.

Molecular endocrinology (Baltimore, Md.) ·Vol. 24 ·No. 4 ·2010-04-00 ·Pages 859-72

Lanz RB, Bulynko Y, Malovannaya A, Labhart P, Wang L, Li W, Qin J, Harper M, O'Malley BW

Abstract

The nuclear receptor and bona fide oncogene, steroid receptor coactivator-3 (SRC-3, AIB1), acts as a master transcriptional regulator of breast cancer by transducing growth signals via the estrogen receptor alpha (ER). In this resource paper, we present the genome-wide localization analysis of SRC-3 chromatin affinity sites in MCF-7 human breast cancer chromatin and compare the cis binding sites to global cartographies for ER and FoxA1. By correlating their gene proximal binding sites to integrated gene expression signatures, and in combination with gene ontology analyses, we provide a functional classification of estradiol-induced gene regulation that further highlights an intricate transcriptional control of interdependent cellular pathways by SRC-3. Furthermore, by presenting proteomics analyses of in vivo SRC-3- and ER-associated proteins, we give strong evidence to support the idea that the interpretative power of SRC-3 in estrogen signaling is mediated through the formation of distinct, cell state-dependent protein complexes. Altogether, we present the first approach in complementary comparative analyses that converges results obtained by three discovery-driven methods (cistromics, transcriptomics, and proteomics) into testable hypotheses, thus providing a valuable resource for follow-up studies that further our understanding of estrogen signaling in human diseases in general and breast cancer in particular.

MeSH Terms
Binding Sites/genetics Blotting, Western Breast Neoplasms/metabolism Cell Line Chromatin/metabolism Chromatin Immunoprecipitation Estradiol/pharmacology Estrogen Receptor alpha/metabolism Genome, Human/genetics Hepatocyte Nuclear Factor 3-alpha/metabolism Humans Nuclear Receptor Coactivator 3/metabolism Polymerase Chain Reaction RNA Interference RNA Polymerase II/metabolism Signal Transduction/drug effects
Chemicals
Chromatin Estrogen Receptor alpha FOXA1 protein, human Hepatocyte Nuclear Factor 3-alpha Estradiol NCOA3 protein, human Nuclear Receptor Coactivator 3 RNA Polymerase II
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Lanz Rainer B
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Bulynko Yaroslava
Malovannaya Anna
Labhart Paul
Wang Liguo
Li Wei
Qin Jun
Harper Mary
O'Malley Bert W
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Article Info
Journal
Molecular endocrinology (Baltimore, Md.)
Abbr.
Mol Endocrinol
ISSN
1944-9917
DOI
10.1210/me.2009-0499
Published
2010-04-00
Epub
2010-00-24
Pages
859-72
Language
English
Region
United States
NLM ID
8801431
PMCID
PMC2852354
Subset
IM
Grants
NIDDK NIH HHS · P01 DK059820 · United States
NCI NIH HHS · P30CA125123 · United States
NIDDK NIH HHS · U19 DK062434 · United States
NICHD NIH HHS · R01 HD008188 · United States
NCI NIH HHS · P30 CA125123 · United States
NIDDK NIH HHS · 5 P01 DK059820 · United States
NICHD NIH HHS · 5 R01 HD08188 · United States
External Links
PubMed source DOI: 10.1210/me.2009-0499 PMC Full Text
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