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

Sanil Patel, Khatanzul Ganbold, Chung Hwan Cho, Juwairriyyah Siddiqui, Ramazan Yildiz, Njeri Sparman, Shani Sadeh, Christy M. Nguyen, Jiexin Wang, Julian P. Whitelegge, Susan K. Fried, Hironori Waki, Claudio J. Villanueva, Marcus M. Seldin, Shinya Sakaguchi, Wilfried Ellmeier, Peter Tontonoz and Prashant Rajbhandari ()
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Sanil Patel: Icahn School of Medicine at Mount Sinai
Khatanzul Ganbold: Icahn School of Medicine at Mount Sinai
Chung Hwan Cho: Icahn School of Medicine at Mount Sinai
Juwairriyyah Siddiqui: Icahn School of Medicine at Mount Sinai
Ramazan Yildiz: Icahn School of Medicine at Mount Sinai
Njeri Sparman: Icahn School of Medicine at Mount Sinai
Shani Sadeh: Icahn School of Medicine at Mount Sinai
Christy M. Nguyen: University of California
Jiexin Wang: University of California
Julian P. Whitelegge: University of California
Susan K. Fried: Icahn School of Medicine at Mount Sinai
Hironori Waki: Akita University
Claudio J. Villanueva: University of California
Marcus M. Seldin: University of California
Shinya Sakaguchi: Institute of Immunology
Wilfried Ellmeier: Institute of Immunology
Peter Tontonoz: University of California
Prashant Rajbhandari: Icahn School of Medicine at Mount Sinai

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-52917-y

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