ArticleMolecular and cellular biology2008
Alternative mechanisms by which mediator subunit MED1/TRAP220 regulates peroxisome proliferator-activated receptor gamma-stimulated adipogenesis and target gene expression.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 95 citations in OpenAlex.
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- Cdo1 promotes PPARγ-mediated adipose tissue lipolysis in male mice.Nature metabolism · 2022Article
- STK38 is a PPARγ-interacting protein promoting adipogenesis.Adipocyte · 2021Article
- Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Energy Homeostasis of Dairy Animals: Exploiting Their Modulation through Nutrigenomic Interventions.International journal of molecular sciences · 2021Review
- Critical roles of transcriptional coactivator MED1 in the formation and function of mouse adipose tissues.Genes & development · 2021Article
- MED1 is a lipogenesis coactivator required for postnatal adipose expansion.Genes & development · 2021Article
- Molecular determinants of MED1 interaction with the DNA bound VDR-RXR heterodimer.Nucleic acids research · 2020Article
- Mediator complex subunit Med19 binds directly GATA transcription factors and is required with Med1 for GATA-driven gene regulationThe Journal of biological chemistry · 2020Article
- MLL3/MLL4-Associated PAGR1 Regulates Adipogenesis by Controlling Induction of C/EBPβ and C/EBPδ.Molecular and cellular biology · 2020Article
- Comparative Transcriptomic Analysis of Subcutaneous Adipose Tissue from Local Pig Breeds.Genes · 2020Article
- Mediator subunit MED1 modulates intranuclear dynamics of the thyroid hormone receptor.Journal of cellular biochemistry · 2020Article
- The transcription factor NKX1-2 promotes adipogenesis and may contribute to a balance between adipocyte and osteoblast differentiation.The Journal of biological chemistry · 2019Article
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- Control of Muscle Metabolism by the Mediator Complex.Cold Spring Harbor perspectives in medicine · 2018Review
- Genome-Wide Variation, Candidate Regions and Genes Associated With Fat Deposition and Tail Morphology in Ethiopian Indigenous Sheep.Frontiers in genetics · 2018Article
5 more citing papers are in PubMed but not listed here.
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9 authors at 4 institutions in 1 country.
Funding
Abstract
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.
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