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Transcriptional control of adipogenesis by PATZ1

Sanil Patel, Njeri Sparman, Shani Sadeh, Jeixin Wang, Julian P. Whitelegge, Susan K. Fried, Hironori Waki, Claudio J. Villanueva, Marcus Seldin, Shinya Sakaguchi, Wilfried Ellmeier, Peter Tontonoz, Prashant Rajbhandari
doi: https://doi.org/10.1101/2022.05.24.493273
Sanil Patel
1Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029 USA
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Njeri Sparman
1Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029 USA
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Shani Sadeh
1Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029 USA
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Jeixin Wang
2Department of Pathology and Laboratory Medicine and Department of Biological Chemistry, University of California, Los Angeles, CA 90095 USA
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Julian P. Whitelegge
3Pasarow Mass Spectrometry Laboratory, NPI-Semel Institute, University of California, Los Angeles, 90095, California, USA
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Susan K. Fried
1Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029 USA
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Hironori Waki
4Department of Diabetes and Metabolic Disease, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Claudio J. Villanueva
5Molecular, Cellular, and Integrative Physiology Program and Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095 USA
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Marcus Seldin
6Department of Biological Chemistry, University of California, Irvine, CA 92697 USA
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Shinya Sakaguchi
7Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
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Wilfried Ellmeier
7Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
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Peter Tontonoz
2Department of Pathology and Laboratory Medicine and Department of Biological Chemistry, University of California, Los Angeles, CA 90095 USA
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Prashant Rajbhandari
1Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029 USA
2Department of Pathology and Laboratory Medicine and Department of Biological Chemistry, University of California, Los Angeles, CA 90095 USA
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  • For correspondence: prashant.rajbhandari@mssm.edu
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Abstract

White 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.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 25, 2022.
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Transcriptional control of adipogenesis by PATZ1
Sanil Patel, Njeri Sparman, Shani Sadeh, Jeixin Wang, Julian P. Whitelegge, Susan K. Fried, Hironori Waki, Claudio J. Villanueva, Marcus Seldin, Shinya Sakaguchi, Wilfried Ellmeier, Peter Tontonoz, Prashant Rajbhandari
bioRxiv 2022.05.24.493273; doi: https://doi.org/10.1101/2022.05.24.493273
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Transcriptional control of adipogenesis by PATZ1
Sanil Patel, Njeri Sparman, Shani Sadeh, Jeixin Wang, Julian P. Whitelegge, Susan K. Fried, Hironori Waki, Claudio J. Villanueva, Marcus Seldin, Shinya Sakaguchi, Wilfried Ellmeier, Peter Tontonoz, Prashant Rajbhandari
bioRxiv 2022.05.24.493273; doi: https://doi.org/10.1101/2022.05.24.493273

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