Global characterization of transcriptional impact of the SRC-3 coregulator.
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.
Lanz
Rainer B
RB
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Bulynko
Yaroslava
Y
Malovannaya
Anna
A
Labhart
Paul
P
Wang
Liguo
L
Li
Wei
W
Qin
Jun
J
Harper
Mary
M
O'Malley
Bert W
BW
D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D015894:Genome, Human / Q000235:genetics; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000378:metabolism; D006801:Humans; D056921:Nuclear Receptor Coactivator 3 / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D012319:RNA Polymerase II / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D002843:Chromatin; D047628:Estrogen Receptor alpha; C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D004958:Estradiol; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3; D012319:RNA Polymerase II