PTIP-associated protein PA1 controls induction of early adipogenic transcription factors

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NIDDK	ENDOC-11

Authors

• J.E. Lee
• Y.W. Cho
• K. Ge

Abstract

Adipogenesis is regulated by sequentially expressed transcription factors. Krox20, KLF4, C/EBPβ and C/EBPδ are induced within hours after initiation and promote expression of master adipogenic regulators PPARγ and C/EBPα. However, the mechanism that controls the induction of these early adipogenic transcription factors remains elusive. PA1 is a component of MLL3/MLL4 histone methyltransferase complex which also contains PTIP. PTIP and PA1 also form separate complex which has been implicated in DNA damage response. However, functions of PTIP and PA1 under normal physiological conditions remain largely unknown. We previously showed that PTIP is required for PPARγ and C/EBPα expression. Here we show that PA1 cooperates with CREB and GR to directly control the induction of four early transcription factors. Deletion of PA1 in preadipocytes prevents the induction of these early factors and leads to severe defects in adipogenesis. Further, deletion of PA1 in adipose tissues in mice significantly reduces tissue weights. Our data suggest an updated model on transcriptional regulation of adipogenesis. PA1 controls induction of four early adipogenic transcription factors. Interestingly, physically interacting PA1 and PTIP control distinct sets of genes during adipogenesis. Importantly, PA1 and PTIP cooperate to control the entire cascade of adipogenic transcription factors that govern adipogenesis.

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