An Evi1-C/EBP? Complex Controls Peroxisome Proliferator-Activated Receptor ?2 Gene Expression To Initiate White Fat Cell Differentiation

• Published in: Molecular and cellular biology Vol. 32; no. 12; pp. 2289 - 2299
• Main Authors: Ishibashi, Jeff, Firtina, Zeynep, Rajakumari, Sona, Wood, Kathleen H, Conroe, Heather M, Steger, David J, Seale, Patrick
• Format: Journal Article
• Language: English
• Published: 01.06.2012
• ISSN: 0270-7306; 1098-5549
• DOI: 10.1128/MCB.06529-11

Fibroblastic preadipocyte cells are recruited to differentiate into new adipocytes during the formation and hyperplastic growth of white adipose tissue. Peroxisome proliferator-activated receptor gamma (PPAR gamma ), 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 gamma 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 gamma levels. Evi1 expression converts nonadipogenic cells into adipocytes via an increase in the predifferentiation levels of PPAR gamma 2, the adipose-selective isoform of PPAR gamma . Conversely, loss of Evi1 in preadipocytes blocks the induction of PPAR gamma 2 and suppresses adipocyte differentiation. Evi1 binds with C/EBP beta to regulatory sites in the Ppar gamma locus at early stages of adipocyte differentiation, coincident with the induction of Ppar gamma 2 expression. These results indicate that Evi1 is a key regulator of adipogenic competency.