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.

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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