TY - JOUR
T1 - MED19 Regulates Adipogenesis and Maintenance of White Adipose Tissue Mass by Mediating PPARγ-Dependent Gene Expression
AU - Dean, John M.
AU - He, Anyuan
AU - Tan, Min
AU - Wang, Jun
AU - Lu, Dongliang
AU - Razani, Babak
AU - Lodhi, Irfan J.
N1 - Publisher Copyright:
© 2020 The Author(s)
PY - 2020/10/6
Y1 - 2020/10/6
N2 - The Mediator complex relays regulatory signals from gene-specific transcription factors to the basal transcriptional machinery. However, the role of individual Mediator subunits in different tissues remains unclear. Here, we demonstrate that MED19 is essential for adipogenesis and maintenance of white adipose tissue (WAT) by mediating peroxisome proliferator-activated receptor gamma (PPARγ) transcriptional activity. MED19 knockdown blocks white adipogenesis, but not brown adipogenesis or C2C12 myoblast differentiation. Adipose-specific MED19 knockout (KO) in mice results in a striking loss of WAT, whitening of brown fat, hepatic steatosis, and insulin resistance. Inducible adipose-specific MED19 KO in adult animals also results in lipodystrophy, demonstrating its requirement for WAT maintenance. Global gene expression analysis reveals induction of genes involved in apoptosis and inflammation and impaired expression of adipose-specific genes, resulting from decreased PPARγ residency on adipocyte gene promoters and reduced association of PPARγ with RNA polymerase II. These results identify MED19 as a crucial facilitator of PPARγ-mediated gene expression in adipose tissue.
AB - The Mediator complex relays regulatory signals from gene-specific transcription factors to the basal transcriptional machinery. However, the role of individual Mediator subunits in different tissues remains unclear. Here, we demonstrate that MED19 is essential for adipogenesis and maintenance of white adipose tissue (WAT) by mediating peroxisome proliferator-activated receptor gamma (PPARγ) transcriptional activity. MED19 knockdown blocks white adipogenesis, but not brown adipogenesis or C2C12 myoblast differentiation. Adipose-specific MED19 knockout (KO) in mice results in a striking loss of WAT, whitening of brown fat, hepatic steatosis, and insulin resistance. Inducible adipose-specific MED19 KO in adult animals also results in lipodystrophy, demonstrating its requirement for WAT maintenance. Global gene expression analysis reveals induction of genes involved in apoptosis and inflammation and impaired expression of adipose-specific genes, resulting from decreased PPARγ residency on adipocyte gene promoters and reduced association of PPARγ with RNA polymerase II. These results identify MED19 as a crucial facilitator of PPARγ-mediated gene expression in adipose tissue.
UR - http://www.scopus.com/inward/record.url?scp=85092327433&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2020.108228
DO - 10.1016/j.celrep.2020.108228
M3 - Article
C2 - 33027649
AN - SCOPUS:85092327433
SN - 2211-1247
VL - 33
JO - Cell Reports
JF - Cell Reports
IS - 1
M1 - 108228
ER -