Transcription factor PATZ1 promotes adipogenesis by controlling promoter regulatory loci of adipogenic factors

• Published in: Nature communications Vol. 15; no. 1; pp. 8533 - 17
• Main Authors: Patel, Sanil, Ganbold, Khatanzul, Cho, Chung Hwan, Siddiqui, Juwairriyyah, Yildiz, Ramazan, Sparman, Njeri, Sadeh, Shani, Nguyen, Christy M, Wang, Jiexin, Whitelegge, Julian P, Fried, Susan K, Waki, Hironori, Villanueva, Claudio J, Seldin, Marcus M, Sakaguchi, Shinya, Ellmeier, Wilfried, Tontonoz, Peter, Rajbhandari, Prashant
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 02.10.2024; Nature Publishing Group UK; Nature Portfolio
• Subjects: 3T3-L1 Cells; Ablation; Adipocytes; Adipocytes - cytology; Adipocytes - metabolism; Adipogenesis; Adipogenesis - genetics; Adipose tissue; Adipose Tissue, White - cytology; Adipose Tissue, White - metabolism; Animal models; Animals; Body fat; Cell culture; Cell Differentiation - genetics; Differentiation; Energy balance; Gene Expression Regulation; Homeostasis; Humans; Lipids; Male; Metabolic disorders; Mice; Mice, Inbred C57BL; Promoter Regions, Genetic - genetics; Protein interaction; Proteins; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Zinc finger proteins
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-52917-y

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.