Transcription factor PATZ1 promotes adipogenesis by controlling promoter regulatory loci of adipogenic factors
Sanil Patel, Khatanzul Ganbold, Chung Hwan Cho, Juwairriyyah Siddiqui, Ramazan Yıldız, Njeri Sparman, Shani Sadeh, Christy M Nguyen, Jiexin Wang, Julian P. Whitelegge, Susan K. Fried, Hironori Waki, Claudio J. Villanueva, Marcus Seldin, Shinya Sakaguchi, Wilfried Ellmeier, Peter Tontonoz, Prashant Rajbhandari
Abstract
White adipose tissue (WAT) is essential for lipid storage and systemic energy homeostasis. Understanding adipocyte formation and stability is key to developing therapies for obesity and metabolic disorders. Through a high-throughput cDNA screen, we identified PATZ1, a POZ/BTB and AT-Hook Containing Zinc Finger 1 protein, as an important adipogenic transcription factor. PATZ1 is expressed in human and mouse adipocyte precursor cells (APCs) and adipocytes. In cellular models, PATZ1 promotes adipogenesis via protein-protein interactions and DNA binding. PATZ1 ablation in mouse adipocytes and APCs leads to a reduced APC pool, decreased fat mass, and hypertrophied adipocytes. ChIP-Seq and RNA-seq analyses show that PATZ1 supports adipogenesis by interacting with transcriptional machinery at the promoter regions of key early adipogenic factors. Mass-spec results show that PATZ1 associates with GTF2I, with GTF2I modulating PATZ1’s function during differentiation. These findings underscore PATZ1’s regulatory role in adipocyte differentiation and adiposity, offering insights into adipose tissue development. Adipogenesis is important for white adipose tissue function. Here the authors identify the transcription factor PATZ1 as a regulator of adipogenesis and adipocyte maintenance, and report that adipose-tissue specific loss of PATZ1 leads to reduced fat mass and larger adipocytes in mice.