An Evi1-C/EBP? complex controls peroxisome proliferator-activated receptor ?2 gene expression to initiate white fat cell differentiation.

ABSTRACT: Fibroblastic preadipocyte cells are recruited to differentiate into new adipocytes during the formation and hyperplastic growth of white adipose tissue. Peroxisome proliferator-activated receptor ? (PPAR?), the master regulator of adipogenesis, is expressed at low levels in preadipocytes, and its levels increase dramatically and rapidly during the differentiation process. However, the mechanisms controlling the dynamic and selective expression of PPAR? in the adipocyte lineage remain largely unknown. We show here that the zinc finger protein Evi1 increases in preadipocytes at the onset of differentiation prior to increases in PPAR? levels. Evi1 expression converts nonadipogenic cells into adipocytes via an increase in the predifferentiation levels of PPAR?2, the adipose-selective isoform of PPAR?. Conversely, loss of Evi1 in preadipocytes blocks the induction of PPAR?2 and suppresses adipocyte differentiation. Evi1 binds with C/EBP? to regulatory sites in the Ppar? locus at early stages of adipocyte differentiation, coincident with the induction of Ppar?2 expression. These results indicate that Evi1 is a key regulator of adipogenic competency.

SUBMITTER: Ishibashi J 

PROVIDER: S-EPMC3372274 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature