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RESEARCH PAPER

Differential gene regulation by the SRC family of coactivators

Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100083, China

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 NFB. 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.

[Keywords: Gene regulation; coactivators; steroid receptors]

Received February 16, 2004; revised version accepted May 21, 2004.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1194704.

¹ These authors contributed equally to this work.

² Corresponding author.
E-MAIL jason{at}bjmu.edu.cn; FAX 86-10-82801355.

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