TY - JOUR
T1 - Critical roles of transcriptional coactivator MED1 in the formation and function of mouse adipose tissues
AU - Ito, Keiichi
AU - Schneeberger, Marc
AU - Gerber, Alan
AU - Jishage, Miki
AU - Marchildon, Francois
AU - Maganti, Aarthi V.
AU - Cohen, Paul
AU - Friedman, Jeffrey M.
AU - Roeder, Robert G.
N1 - Funding Information:
We thank Sohail Malik and Mitsuhiro Ito for comments on the manuscript; Satoshi Iida, Tomoyoshi Nakadai, Wei Chen, and Sicong Zhang for discussion of the work; and Yoko Tajima for assistance with data presentation using R. We thank Dr. Janardan Reddy for kindly providing Med1 conditional knockout mouse. We thank the Rockefeller University Flow Cytometry Resource Center, Henrik Molina, and the Proteomics Core Facility at the Rockefeller University for mass spectrometry; Christina Pyrgaki and the Bioimaging Resource Center at the Rockefeller University for adipose tissue imaging; Rada Norinsky, Roxana Cubias, and the Rockefeller University Transgenic and Reproductive Technology Center for the derivation of the Med1-null mouse from frozen sperm; the Rockefeller University Genomics Core Facility for microarray analysis; and the Laboratory of Comparative Pathology at the Memorial Sloan Kettering Cancer Center for histology studies. This work was supported by National Institutes of Health grants DK071900 and CA234575 to R.G.R. K.I. was supported by National Cancer Institute T32 grant CA009673 and by a Japan Society for the Promotion of Science postdoctoral fellowship for research abroad.
Publisher Copyright:
© 2021 Cold Spring Harbor Laboratory Press. All rights reserved.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - The MED1 subunit has been shown to mediate ligand-dependent binding of the Mediator coactivator complex to multiple nuclear receptors, including the adipogenic PPAR, and to play an essential role in ectopic PPAR-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, maintenance, 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 homeostatic functions of adipocytes.
AB - The MED1 subunit has been shown to mediate ligand-dependent binding of the Mediator coactivator complex to multiple nuclear receptors, including the adipogenic PPAR, and to play an essential role in ectopic PPAR-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, maintenance, 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 homeostatic functions of adipocytes.
KW - MED1
KW - Mediator complex
KW - adipogenesis
KW - coactivator
KW - development
KW - embryonic stem cell
KW - lipodystrophy
KW - thermogenesis
KW - transcriptional regulation
UR - http://www.scopus.com/inward/record.url?scp=85106062482&partnerID=8YFLogxK
U2 - 10.1101/gad.346791.120
DO - 10.1101/gad.346791.120
M3 - Article
C2 - 33888560
VL - 35
SP - 729
EP - 748
JO - Genes & Development
JF - Genes & Development
IS - 9-10
ER -