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 Citations (Scopus)

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

Fingerprint

Steroid Receptors
Nuclear Receptor Coactivator 1
Genes
Nuclear Receptor Coactivators
Hormones
Breast Neoplasms
Gene Knockout Techniques
Proteins
Knockout Mice
Carcinogenesis
Transcription Factors

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., ... 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

Differential gene regulation by the SRC family of coactivators. / Zhang, Hua; Yi, Xia; Sun, Xiaojing; Yin, Na; Shi, Bin; Wu, Huijian; Wang, Dan; Wu, Ge; Shang, Yongfeng.

In: Genes and Development, Vol. 18, No. 14, 15.07.2004, p. 1753-1765.

Research output: Contribution to journalArticle

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, vol. 18, no. 14, pp. 1753-1765. https://doi.org/10.1101/gad.1194704
Zhang, Hua ; Yi, Xia ; Sun, Xiaojing ; Yin, Na ; Shi, Bin ; Wu, Huijian ; Wang, Dan ; Wu, Ge ; Shang, Yongfeng. / Differential gene regulation by the SRC family of coactivators. In: Genes and Development. 2004 ; Vol. 18, No. 14. pp. 1753-1765.
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