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MED1 is a lipogenesis co-activator required for postnatal adipose expansion

ABSTRACT: MED1 often serves as a surrogate of the general transcription coactivator complex Mediator for identifying active enhancers. MED1 is required for phenotypic conversion of fibroblasts to adipocytes in vitro but its role in adipose development and expansion in vivo has not been reported. Here we show that MED1 is not generally required for transcription during adipogenesis in culture and that MED1 is dispensable for adipose development in mice. Instead, MED1 is required for postnatal adipose expansion and the induction of fatty acid and triglyceride synthesis genes after pups switch diet from high-fat maternal milk to carbohydrate-based chow. During adipogenesis, MED1 is dispensable for induction of lineage-determining transcription factors (TFs) PPARγ and C/EBPα but is required for lipid accumulation in the late phase of differentiation. Mechanistically, MED1 controls the induction of lipogenesis genes by facilitating lipogenic TF ChREBP- and SREBP1a-dependent recruitment of Mediator to active enhancers. Together, our ﬁndings identify a cell- and gene-specific regulatory role of MED1 as a lipogenesis coactivator required for postnatal adipose expansion.

ORGANISM(S): Mus musculus

PROVIDER: GSE160605 | GEO | 2021/03/17

REPOSITORIES: GEO

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Gene expression data from differentiating 3T3-L1 cells

Project description:The MED1 subunit has been shown to mediate ligand-dependent binding of the Mediator coactivator complex to multiple nuclear receptors, including the adipogenic PPARγ, and to play an essential role in ectopic PPARγ-induced adipogenesis of mouse embryonic fibroblasts. However, the precise roles of MED1, and its various domains, at various stages of adipogenesis and in adipose tissue have been unclear. Here, after establishing requirements for MED1, including specific domains, for differentiation of 3T3L1 cells and both primary white and brown preadipocytes, we used multiple genetic approaches to assess requirements for MED1 in adipocyte formation and function in mice. We show that MED1 is indeed essential for the differentiation and/or function of both brown and white adipocytes, as its absence in these cells leads to, respectively, defective brown fat function and lipodystrophy. This work establishes MED1 as an essential transcriptional coactivator that ensures the formation and homeostatic functions of adipocytes.

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MED1 is a lipogenesis co-activator required for postnatal adipose expansion

Project description:MED1 is a lipogenesis co-activator required for postnatal adipose expansion

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GR accelerates, but is largely dispensable for, adipogenesis

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Ablation of coactivator Med1 regulates bulge keratinocyte stem cells and accelerates epidermal regeneration after injury [10wk skin]

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Ablation of coactivator Med1 regulates bulge keratinocyte stem cells and accelerates epidermal regeneration after injury [skin wound]

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2014-01-01 | E-GEOD-50670 | biostudies-arrayexpress

Ablation of coactivator Med1 regulates bulge keratinocyte stem cells and accelerates epidermal regeneration after injury [10wk keratinocyte]

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2014-01-01 | E-GEOD-50672 | biostudies-arrayexpress

Ablation of coactivator Med1 regulates bulge keratinocyte stem cells and accelerates epidermal regeneration after injury [10wk keratinocyte]

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