Differential gene regulation by the SRC family of coactivators

Hua Zhang, Xia Yi, Xiaojing Sun, Na Yin, Bin Shi, Huijian Wu, Dan Wang, Ge Wu, Yongfeng Shang

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

SRCs (steroid receptor coactivators) are required for nuclear receptor-mediated transcription and are also implicated in the transcription initiation by other transcription factors, such as STATs and NFκB. Despite phenotypic manifestations in gene knockout mice for SRC-1, GRIP1, and AIB1 of the SRC (Steroid Receptor Coactivator) family indicating their differential roles in animal physiology, there is no clear evidence, at the molecular level, to support a functional specificity for these proteins. We demonstrated in this report that two species of SRC coactivators, either as AIB1:GRIP1 or as AIB1:SRC-1 are recruited, possibly through heterodimerization, on the promoter of genes that contain a classical hormone responsive element (HRE). In contrast, on non-HRE-containing gene promoters, on which steroid receptors bind indirectly, either GRIP1 or SRC-1 is recruited as a monomer, depending on the cellular abundance of the protein. Typically, non-HRE-containing genes are early genes activated by steroid receptors, whereas HRE-containing genes are activated later. Our results also showed that SRC proteins contribute to the temporal regulation of gene transcription. In addition, our experiments revealed a positive correlation between AIB1/c-myc overexpression in ER+ breast carcinoma samples, suggesting a possible mechanism for AIB1 in breast cancer carcinogenesis.

Original languageEnglish (US)
Pages (from-to)1753-1765
Number of pages13
JournalGenes and Development
Volume18
Issue number14
DOIs
StatePublished - Jul 15 2004

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Keywords

  • Coactivators
  • Gene regulation
  • Steroid receptors

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Zhang, H., Yi, X., Sun, X., Yin, N., Shi, B., Wu, H., Wang, D., Wu, G., & Shang, Y. (2004). Differential gene regulation by the SRC family of coactivators. Genes and Development, 18(14), 1753-1765. https://doi.org/10.1101/gad.1194704