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PMID: 17967894 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

STAGA recruits Mediator to the MYC oncoprotein to stimulate transcription and cell proliferation.

Molecular and cellular biology ·Vol. 28 ·No. 1 ·2008-01-00 ·Pages 108-21

Liu X, Vorontchikhina M, Wang YL, Faiola F, Martinez E

Abstract

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 STAF65gamma 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. STAF65gamma 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 STAF65gamma-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.

MeSH Terms
Acetylesterase/genetics,metabolism Cell Line Cell Proliferation DNA-Binding Proteins/genetics,metabolism Humans Multiprotein Complexes/chemistry,metabolism Oncogene Protein p55(v-myc)/genetics,metabolism Promoter Regions, Genetic/genetics Protein Binding TATA-Binding Protein Associated Factors/genetics,metabolism Telomerase/genetics,metabolism Trans-Activators/genetics,metabolism Transcription Factor TFIID/genetics,metabolism Transcription Factors/genetics,metabolism Transcription, Genetic p300-CBP Transcription Factors/genetics,metabolism
Chemicals
DNA-Binding Proteins Multiprotein Complexes Oncogene Protein p55(v-myc) SUPT3H protein, human TAF9 protein, human TATA-Binding Protein Associated Factors Trans-Activators Transcription Factor TFIID Transcription Factors ZNF143 protein, human p300-CBP Transcription Factors p300-CBP-associated factor TERT protein, human Telomerase Acetylesterase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Liu Xiaohui
Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA.
Vorontchikhina Marina
Wang Yuan-Liang
Faiola Francesco
Martinez Ernest
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
DOI
10.1128/MCB.01402-07
Published
2008-01-00
Epub
2007-00-29
Pages
108-21
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2223283
Subset
IM
Grants
NCI NIH HHS · R01 CA100464 · United States
NCI NIH HHS · CA100464 · United States
External Links
PubMed source DOI: 10.1128/MCB.01402-07 PMC Full Text View journal details
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