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Molecular and Cellular Biology, January 2009, p. 315-323, Vol. 29, No. 2
0270-7306/09/$08.00+0     doi:10.1128/MCB.00347-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Mat1 Inhibits Peroxisome Proliferator-Activated Receptor {gamma}-Mediated Adipocyte Differentiation{triangledown} ,{dagger}

Katja Helenius, Ying Yang, Jukka Alasaari, and Tomi P. Mäkelä*

Genome-Scale Biology Program and Institute of Biomedicine, Biomedicum Helsinki, 00014 University of Helsinki, Helsinki, Finland

Received 29 February 2008/ Returned for modification 28 April 2008/ Accepted 24 October 2008

Mammalian Cdk7, cyclin H, and Mat1 form the kinase submodule of transcription factor IIH (TFIIH) and have been considered ubiquitously expressed elements of the transcriptional machinery. Here we found that Mat1 and Cdk7 levels are undetectable in adipose tissues in vivo and downregulated during adipogenesis, where activation of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) acts as a critical differentiation switch. Using both Mat1–/– mouse embryonic fibroblasts and Cdk7 knockdown approaches, we show that the Cdk7 complex is an inhibitor of adipogenesis and is required for inactivation of PPAR{gamma} through the phosphorylation of PPAR{gamma}-S112. The results demonstrate that the Cdk7 submodule of TFIIH acts as a physiological roadblock to adipogenesis by inhibiting PPAR{gamma} activity. The observation that components of TFIIH are absent from transcriptionally active adipose tissue prompts a reevaluation of the ubiquitous nature of basal transcription factors in mammalian tissues.

* Corresponding author. Mailing address: Genome-Scale Biology Program and Institute of Biomedicine, Biomedicum Helsinki, 00014 University of Helsinki, Helsinki, Finland. Phone: 358-9-1912 5555. Fax: 358-9-1912 5554. E-mail: Tomi.Makela{at}helsinki.fi

{triangledown} Published ahead of print on 3 November 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, January 2009, p. 315-323, Vol. 29, No. 2
0270-7306/09/$08.00+0     doi:10.1128/MCB.00347-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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