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Updated: Jun 15, 2026

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
Global characterization of transcriptional impact of the SRC-3 coregulator
Rainer B Lanz1, Yaroslava Bulynko, Anna Malovannaya
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
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.
Insights
Steroid receptor coactivator-3 (SRC-3) regulates breast cancer growth by controlling genes through estrogen receptor alpha (ER). This study maps SRC-3
Area of Science:
- Molecular Biology
- Genomics
- Oncology
Background:
- Steroid receptor coactivator-3 (SRC-3), also known as AIB1, is a key oncogene regulating breast cancer.
- SRC-3 acts as a master transcriptional regulator, mediating growth signals through estrogen receptor alpha (ER).
Purpose of the Study:
- To perform a genome-wide localization analysis of SRC-3 chromatin binding sites in human breast cancer cells.
- To compare SRC-3 binding sites with those of ER and FoxA1.
- To functionally classify estradiol-induced gene regulation and understand SRC-3's role in estrogen signaling.
Main Methods:
- Genome-wide chromatin localization analysis (cistromics) of SRC-3 in MCF-7 cells.
- Comparative analysis of SRC-3, ER, and FoxA1 cis-binding sites.
- Integration of binding site data with gene expression signatures and gene ontology analysis.
- Proteomics analysis to identify SRC-3 and ER-associated proteins.
Main Results:
- Identification of SRC-3 chromatin affinity sites and comparison with ER and FoxA1 binding profiles.
- Functional classification of estradiol-induced genes, revealing intricate transcriptional control by SRC-3.
- Proteomic evidence supporting SRC-3's role in estrogen signaling through distinct protein complexes.
Conclusions:
- SRC-3 plays a critical role in transcriptional regulation of estrogen-responsive genes in breast cancer.
- SRC-3 mediates estrogen signaling via cell state-dependent protein complexes.
- This study provides a valuable resource for understanding estrogen signaling in breast cancer and other human diseases.
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