Global characterization of transcriptional impact of the SRC-3 coregulator

Rainer B. Lanz, Yaroslava Bulynko, Anna Malovannaya, Paul Labhart, Liguo Wang, Wei Li, Jun Qin, Mary Harper, Bert W. O'Malley

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38 Scopus citations

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 α (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.

Original languageEnglish (US)
Pages (from-to)859-872
Number of pages14
JournalMolecular Endocrinology
Volume24
Issue number4
DOIs
StatePublished - Apr 1 2010

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ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Lanz, R. B., Bulynko, Y., Malovannaya, A., Labhart, P., Wang, L., Li, W., Qin, J., Harper, M., & O'Malley, B. W. (2010). Global characterization of transcriptional impact of the SRC-3 coregulator. Molecular Endocrinology, 24(4), 859-872. https://doi.org/10.1210/me.2009-0499