Mat1 inhibits peroxisome proliferator-activated receptor gamma-mediated adipocyte differentiation.
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 (PPARgamma) 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 PPARgamma through the phosphorylation of PPARgamma-S112. The results demonstrate that the Cdk7 submodule of TFIIH acts as a physiological roadblock to adipogenesis by inhibiting PPARgamma 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.
Helenius
Katja
K
Genome-Scale Biology Program and Institute of Biomedicine, Biomedicum Helsinki, 00014 University of Helsinki, Helsinki, Finland.
Yang
Ying
Y
Alasaari
Jukka
J
Mäkelä
Tomi P
TP
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D002455:Cell Division; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D047495:PPAR gamma / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D012694:Serine; D051758:Transcription Factor TFIIH / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D026921:Amino Acid Transport Systems, Neutral; D018797:Cell Cycle Proteins; D018844:Cyclin-Dependent Kinases; D047495:PPAR gamma; D012694:Serine; D051758:Transcription Factor TFIIH; D014157:Transcription Factors; D000095043:Cyclin-Dependent Kinase-Activating Kinase; C432410:Mnat1 protein, mouse; C090586:Cdk7 protein, mouse