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

Research output: Contribution to journalArticle

36 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Breast Neoplasms
Estrogen Receptors
Proteomics
Chromatin
Nuclear Receptor Coactivator 3
Estrogens
Binding Sites
Gene Ontology
Cytoplasmic and Nuclear Receptors
Oncogenes
Transcriptome
Genes
Estradiol
Genome
Growth
Proteins
estrophilin

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Lanz, R. B., Bulynko, Y., Malovannaya, A., Labhart, P., Wang, L., Li, W., ... 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

Global characterization of transcriptional impact of the SRC-3 coregulator. / Lanz, Rainer B.; Bulynko, Yaroslava; Malovannaya, Anna; Labhart, Paul; Wang, Liguo; Li, Wei; Qin, Jun; Harper, Mary; O'Malley, Bert W.

In: Molecular Endocrinology, Vol. 24, No. 4, 01.04.2010, p. 859-872.

Research output: Contribution to journalArticle

Lanz, RB, Bulynko, Y, Malovannaya, A, Labhart, P, Wang, L, Li, W, Qin, J, Harper, M & O'Malley, BW 2010, 'Global characterization of transcriptional impact of the SRC-3 coregulator', Molecular Endocrinology, vol. 24, no. 4, pp. 859-872. https://doi.org/10.1210/me.2009-0499
Lanz, Rainer B. ; Bulynko, Yaroslava ; Malovannaya, Anna ; Labhart, Paul ; Wang, Liguo ; Li, Wei ; Qin, Jun ; Harper, Mary ; O'Malley, Bert W. / Global characterization of transcriptional impact of the SRC-3 coregulator. In: Molecular Endocrinology. 2010 ; Vol. 24, No. 4. pp. 859-872.
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