Critical roles of transcriptional coactivator MED1 in the formation and function of mouse adipose tissues.
3T3-L1 Cells
Adipocytes
/ cytology
Adipose Tissue, Brown
/ metabolism
Adipose Tissue, White
/ metabolism
Animals
Cell Differentiation
/ genetics
Cells, Cultured
Embryonic Stem Cells
/ cytology
Gene Expression Regulation, Developmental
/ genetics
Mediator Complex
/ genetics
Mediator Complex Subunit 1
/ genetics
Mice
Protein Binding
/ genetics
Protein Domains
MED1
Mediator complex
adipogenesis
coactivator
development
embryonic stem cell
lipodystrophy
thermogenesis
transcriptional regulation
Journal
Genes & development
ISSN: 1549-5477
Titre abrégé: Genes Dev
Pays: United States
ID NLM: 8711660
Informations de publication
Date de publication:
01 05 2021
01 05 2021
Historique:
received:
08
11
2020
accepted:
16
03
2021
pubmed:
24
4
2021
medline:
18
9
2021
entrez:
23
4
2021
Statut:
ppublish
Résumé
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, 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.
Identifiants
pubmed: 33888560
pii: gad.346791.120
doi: 10.1101/gad.346791.120
pmc: PMC8091968
doi:
Substances chimiques
Med1 protein, mouse
0
Mediator Complex
0
Mediator Complex Subunit 1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
729-748Subventions
Organisme : NCI NIH HHS
ID : R01 CA234575
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK071900
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020541
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009673
Pays : United States
Organisme : NIDDK NIH HHS
ID : P60 DK020541
Pays : United States
Informations de copyright
© 2021 Ito et al.; Published by Cold Spring Harbor Laboratory Press.
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