Alternative Mechanisms by Which Mediator Subunit MED1/TRAP220 Regulates Peroxisome Proliferator-Activated Receptor {gamma}-Stimulated Adipogenesis and Target Gene Expression.

Alternative Mechanisms by Which Mediator Subunit MED1/TRAP220 Regulates Peroxisome Proliferator-Activated Receptor {gamma}-Stimulated Adipogenesis and Target Gene Expression. Research Abstract Details 

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Alternative Mechanisms by Which Mediator Subunit MED1/TRAP220 Regulates Peroxisome Proliferator-Activated Receptor {gamma}-Stimulated Adipogenesis and Target Gene Expression. Abstract Text:

Kai Ge,Young-Wook Cho,Hong Guo,Teresa B Hong,Mohamed Guermah,Mitsuhiro Ito,Hong Yu,Markus Kalkum,Robert G Roeder,Kai Ge,Young-Wook Cho,Hong Guo,Teresa B Hong,Mohamed Guermah,Mitsuhiro Ito,Hong Yu,Markus Kalkum,Robert G Roeder,

Mediator is a general coactivator complex connecting transcription activators and RNA polymerase II. Recent work has shown that the nuclear receptor-interacting MED1/TRAP220 subunit of Mediator is required for peroxisome proliferator-activated receptor gamma (PPARgamma)-stimulated adipogenesis of mouse embryonic fibroblasts (MEFs). However, the molecular mechanisms remain undefined. Here, we show an intracellular PPARgamma-Mediator interaction that requires the two LXXLL nuclear receptor recognition motifs on MED1/TRAP220 and, furthermore, we show that the intact LXXLL motifs are essential for optimal PPARgamma function in a reconstituted cell-free transcription system. Surprisingly, a conserved N-terminal region of MED1/TRAP220 that lacks the LXXLL motifs but gets incorporated into Mediator fully supports PPARgamma-stimulated adipogenesis. Moreover, in undifferentiated MEFs, MED1/TRAP220 is dispensable both for PPARgamma-mediated target gene activation and for recruitment of Mediator to a PPAR response element on the aP2 target gene promoter. However, PPARgamma shows significantly reduced transcriptional activity in cells deficient for a subunit (MED24/TRAP100) important for the integrity of the Mediator complex, indicating a general Mediator requirement for PPARgamma function. These results indicate that there is a conditional requirement for MED1/TRAP220 and that a direct interaction between PPARgamma and Mediator through MED1/TRAP220 is not essential either for PPARgamma-stimulated adipogenesis or for PPARgamma target gene expression in cultured fibroblasts. As Mediator is apparently essential for PPARgamma transcriptional activity, our data indicate the presence of alternative mechanisms for Mediator recruitment, possibly through intermediate cofactors or other cofactors that are functionally redundant with MED1/TRAP220.

Alternative Mechanisms by Which Mediator Subunit MED1/TRAP220 Regulates Peroxisome Proliferator-Activated Receptor {gamma}-Stimulated Adipogenesis and Target Gene Expression. Publishing Authors By Initials

K Ge,YW Cho,H Guo,TB Hong,M Guermah,M Ito,H Yu,M Kalkum,RG Roeder,K Ge,YW Cho,H Guo,TB Hong,M Guermah,M Ito,H Yu,M Kalkum,RG Roeder,

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Alternative Mechanisms by Which Mediator Subunit MED1/TRAP220 Regulates Peroxisome Proliferator-Activated Receptor {gamma}-Stimulated Adipogenesis and Target Gene Expression. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Molecular and cellular biology

VOLUME: 28

Page Numbers: 1081-91

Journal Abbreviation: Mol. Cell. Biol.

ISSN: 1098-5549

DAY: 26

MONTH: 11

YEAR: 2007

Alternative Mechanisms by Which Mediator Subunit MED1/TRAP220 Regulates Peroxisome Proliferator-Activated Receptor {gamma}-Stimulated Adipogenesis and Target Gene Expression. Information

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LANGUAGE: eng

NlmUniqueID: 8109087

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AFFILIATION: Building 10, Room 8N307C, NIH, Bethesda, MD 20892. kaig@niddk.nih.gov.

Country: United States

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MEDLINETA: Mol Cell Biol

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