Transcriptional control of adipogenesis by PATZ1

Abstract

AbstractWhite adipose tissues (WAT) play a central role in lipid storage and systemic energy, lipid, and glucose homeostasis. Understanding the intricacies of adipocyte formation could inform therapies for obesity and metabolic disorders. We have identified the POZ/BTB and AT Hook Containing Zinc Finger 1 (PATZ1) protein as an adipogenic transcription factor through an unbiased high-throughput cDNA screen for modulators of adipogenesis. PATZ1 is expressed by both human and mouse adipocyte precursor cells (APC) and adipocytes, and its expression negatively correlates with obesity. In cell models, PATZ1 expression promotes adipogenesis through a mechanism dependent on protein-protein interaction and DNA binding. Adipose-specific ablation of PATZ1 in mice leads to decreased lipid storage and fat mass and protection from diet-induced obesity. Genome-wide PATZ1 DNA binding analyses using ChIP-Seq suggest that PATZ1 facilitates adipogenesis through interactions with transcription factor machinery at the promoter regions of key adipogenic factors and histone modifiers. Global PATZ1 protein interaction studies using immunoprecipitation-mass spectrometry (IP-MS) suggest that General Transcription Factor 2I (GTF2I) binding to PATZ1 forms a repressive complex, and knockdown of GTF2I augments PATZ1 adipogenic function. Collectively these findings identify PATZ1 as a regulator of the adipocyte differentiation programs and advance our understanding of the complex transcriptional mechanisms underlying adipose tissue development and homeostasis.