Transcription factor PATZ1 promotes adipogenesis by controlling promoter regulatory loci of adipogenic factors
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.
Authors
- Shinya Sakaguchi (ORCID: https://orcid.org/0000-0002-0591-2469)
- Hironori Waki (ORCID: https://orcid.org/0000-0002-5302-9793)
- Wilfried Ellmeier (ORCID: https://orcid.org/0000-0001-8192-8481)
- Sanil Patel (ORCID: https://orcid.org/0009-0002-7874-1063)
- Njeri Sparman
- Claudio J. Villanueva (ORCID: https://orcid.org/0000-0002-9731-7463)
- Christy M Nguyen (ORCID: https://orcid.org/0000-0002-3897-6207)
- Chung Hwan Cho (ORCID: https://orcid.org/0000-0001-9666-5311)
- Peter Tontonoz (ORCID: https://orcid.org/0000-0003-1259-0477)
- Marcus Seldin (ORCID: https://orcid.org/0000-0001-8026-4759)
- Ramazan Yıldız (ORCID: https://orcid.org/0000-0001-5772-0891)
- Prashant Rajbhandari (ORCID: https://orcid.org/0000-0002-8146-3861)
- Shani Sadeh (ORCID: https://orcid.org/0000-0002-6892-7043)
- Julian P. Whitelegge (ORCID: https://orcid.org/0000-0003-2763-7733)
- Susan K. Fried (ORCID: https://orcid.org/0000-0003-1101-9332)
- Jiexin Wang (ORCID: https://orcid.org/0000-0003-1697-1242)
- Khatanzul Ganbold
- Juwairriyyah Siddiqui
Institutions
- House Clinic (US)
- University of California, Los Angeles (US)
- Akita University (JP)
- University of California, Irvine (US)
- Laboratoire d’immunologie intégrative du cancer (FR)
- Medical University of Vienna (AT)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-02
- DOI
- https://doi.org/10.1038/s41467-024-52917-y
- Citations
- 11
- Primary Topic
- Adipose Tissue and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 3.59
Funders
- Austrian Science Fund
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases
- Division of Cancer Epidemiology and Genetics, National Cancer Institute