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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]

Project description:Transcriptional coactivator Mediator complex facilitates transcription of various transcription factors. Previously, we have generated Med1 conditional null mice, where a critical subunit of Mediator, Med1, is removed from keratinocytes. Here we present evidence that ablation of Med1 accelerated epidermal regeneration after injury. As bulge keratinocyte stem cells are important contributors to regenerate epidermis, we first analyzed properties of stem cells in Med1 null mice. BrdU long retaining analysis revealed that deletion of Med1 still maintained quiescence of bulge keratinocyte stem cells, despite of general hyperplasia observed in Med1 deficient keratinocytes. Gene expression analysis demonstrated that a series of niche matrix proteins decreased in Med1 deficient keratinocytes. In contrast, the expression of stem cell marker Sox9 was not altered, suggesting stem cells are present but activated because of abnormal niche surrounding stem cells. In addition, Med1 deletion suppressed injury induced inflammatory reaction, which indirectly regulates epidermal regeneration. We also indicated that TGFβ1 significantly decreased in both bulge and epidermal keratinocytes upon Med1 deletion. Our study demonstrates that coactivator Med1 has a critical role to maintain bulge stem cells and epidermal regeneration presumably through regulation in TGFβ signaling. n=4 WT and KO (each sample contain RNA from one mouse)

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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 [skin wound]

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