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Molecular and Cellular Biology, January 2008, p. 108-121, Vol. 28, No. 1
0270-7306/08/$08.00+0     doi:10.1128/MCB.01402-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

STAGA Recruits Mediator to the MYC Oncoprotein To Stimulate Transcription and Cell Proliferation{triangledown}

Xiaohui Liu, Marina Vorontchikhina, Yuan-Liang Wang, Francesco Faiola, and Ernest Martinez*

Department of Biochemistry, University of California, Riverside, California 92521

Received 3 August 2007/ Returned for modification 24 September 2007/ Accepted 10 October 2007

Activation of eukaryotic gene transcription involves the recruitment by DNA-binding activators of multiprotein histone acetyltransferase (HAT) and Mediator complexes. How these coactivator complexes functionally cooperate and the roles of the different subunits/modules remain unclear. Here we report physical interactions between the human HAT complex STAGA (SPT3-TAF9-GCN5-acetylase) and a "core" form of the Mediator complex during transcription activation by the MYC oncoprotein. Knockdown of the STAF65{gamma} component of STAGA in human cells prevents the stable association of TRRAP and GCN5 with the SPT3 and TAF9 subunits; impairs transcription of MYC-dependent genes, including MYC transactivation of the telomerase reverse transcriptase (TERT) promoter; and inhibits proliferation of MYC-dependent cells. STAF65{gamma} is required for SPT3/STAGA interaction with core Mediator and for MYC recruitment of SPT3, TAF9, and core Mediator components to the TERT promoter but is dispensable for MYC recruitment of TRRAP, GCN5, and p300 and for acetylation of nucleosomes and loading of TFIID and RNA polymerase II on the promoter. These results suggest a novel STAF65{gamma}-dependent function of STAGA-type complexes in cell proliferation and transcription activation by MYC postloading of TFIID and RNA polymerase II that involves direct recruitment of core Mediator.

* Corresponding author. Mailing address: Department of Biochemistry, University of California, Riverside, Riverside, CA 92521. Phone: (951) 827 2031. Fax: (951) 827 4434. E-mail: ernest.martinez{at}ucr.edu

{triangledown} Published ahead of print on 27 October 2007.

Molecular and Cellular Biology, January 2008, p. 108-121, Vol. 28, No. 1
0270-7306/08/$08.00+0     doi:10.1128/MCB.01402-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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