4.7 Article

MED1 is a lipogenesis coactivator required for postnatal adipose expansion

Journal

GENES & DEVELOPMENT
Volume 35, Issue 9-10, Pages 713-728

Publisher

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.347583.120

Keywords

MED1; Mediator; adipose expansion; coactivator; de novo lipogenesis]

Funding

  1. Intramural Research Program of NIDDK, National Institutes of Health

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Our study reveals that MED1 is not generally required for transcription during adipogenesis, but plays a crucial role in postnatal adipose expansion and induction of lipid synthesis genes after diet switch.
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) PPAR gamma and C/EBP alpha 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.

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