ResearchIn-Press PreviewMetabolism Open Access | 10.1172/jci.insight.164771
1Department of Biology, Georgia State University, Atlanta, United States of America
2Department of Medicine, Albert Einstein College of Medicine, Bronx, United States of America
3Department of Medicine, University of Maryland School of Medicine, Baltimore, United States of America
4Georgia Cancer Center, Augusta University, Augusta, United States of America
5Department of Biology, Geogia State University, Atlanta, United States of America
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1Department of Biology, Georgia State University, Atlanta, United States of America
2Department of Medicine, Albert Einstein College of Medicine, Bronx, United States of America
3Department of Medicine, University of Maryland School of Medicine, Baltimore, United States of America
4Georgia Cancer Center, Augusta University, Augusta, United States of America
5Department of Biology, Geogia State University, Atlanta, United States of America
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1Department of Biology, Georgia State University, Atlanta, United States of America
2Department of Medicine, Albert Einstein College of Medicine, Bronx, United States of America
3Department of Medicine, University of Maryland School of Medicine, Baltimore, United States of America
4Georgia Cancer Center, Augusta University, Augusta, United States of America
5Department of Biology, Geogia State University, Atlanta, United States of America
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1Department of Biology, Georgia State University, Atlanta, United States of America
2Department of Medicine, Albert Einstein College of Medicine, Bronx, United States of America
3Department of Medicine, University of Maryland School of Medicine, Baltimore, United States of America
4Georgia Cancer Center, Augusta University, Augusta, United States of America
5Department of Biology, Geogia State University, Atlanta, United States of America
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1Department of Biology, Georgia State University, Atlanta, United States of America
2Department of Medicine, Albert Einstein College of Medicine, Bronx, United States of America
3Department of Medicine, University of Maryland School of Medicine, Baltimore, United States of America
4Georgia Cancer Center, Augusta University, Augusta, United States of America
5Department of Biology, Geogia State University, Atlanta, United States of America
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1Department of Biology, Georgia State University, Atlanta, United States of America
2Department of Medicine, Albert Einstein College of Medicine, Bronx, United States of America
3Department of Medicine, University of Maryland School of Medicine, Baltimore, United States of America
4Georgia Cancer Center, Augusta University, Augusta, United States of America
5Department of Biology, Geogia State University, Atlanta, United States of America
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1Department of Biology, Georgia State University, Atlanta, United States of America
2Department of Medicine, Albert Einstein College of Medicine, Bronx, United States of America
3Department of Medicine, University of Maryland School of Medicine, Baltimore, United States of America
4Georgia Cancer Center, Augusta University, Augusta, United States of America
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1Department of Biology, Georgia State University, Atlanta, United States of America
2Department of Medicine, Albert Einstein College of Medicine, Bronx, United States of America
3Department of Medicine, University of Maryland School of Medicine, Baltimore, United States of America
4Georgia Cancer Center, Augusta University, Augusta, United States of America
5Department of Biology, Geogia State University, Atlanta, United States of America
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1Department of Biology, Georgia State University, Atlanta, United States of America
2Department of Medicine, Albert Einstein College of Medicine, Bronx, United States of America
3Department of Medicine, University of Maryland School of Medicine, Baltimore, United States of America
4Georgia Cancer Center, Augusta University, Augusta, United States of America
5Department of Biology, Geogia State University, Atlanta, United States of America
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1Department of Biology, Georgia State University, Atlanta, United States of America
2Department of Medicine, Albert Einstein College of Medicine, Bronx, United States of America
3Department of Medicine, University of Maryland School of Medicine, Baltimore, United States of America
4Georgia Cancer Center, Augusta University, Augusta, United States of America
5Department of Biology, Geogia State University, Atlanta, United States of America
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1Department of Biology, Georgia State University, Atlanta, United States of America
2Department of Medicine, Albert Einstein College of Medicine, Bronx, United States of America
3Department of Medicine, University of Maryland School of Medicine, Baltimore, United States of America
4Georgia Cancer Center, Augusta University, Augusta, United States of America
5Department of Biology, Geogia State University, Atlanta, United States of America
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Published May 7, 2024 - More info
Activation of brown adipose tissue (BAT) thermogenesis increases energy expenditure and alleviates obesity. Here we discover that histone methyltransferase suppressor of variegation 4-20 homolog 2 (Suv420h2) expression parallels that of Ucp1 in brown and beige adipocytes and that Suv420h2 knockdown significantly reduces, whereas Suv420h2 overexpression significantly increases Ucp1 levels in brown adipocytes. Suv420h2 knockout (H2KO) mice exhibit impaired cold-induced thermogenesis and are prone to diet-induced obesity. In contrast, mice with specific overexpression of Suv420h2 in adipocytes display enhanced cold-induced thermogenesis and are resistant to diet-induced obesity. Further study shows that Suv420h2 catalyzes H4K20 trimethylation at eukaryotic translation initiation factor 4E-binding protein 1 (4e-bp1) promoter, leading to down-regulated expression of 4e-bp1, a negative regulator of the translation initiation complex. This in turn up-regulates PGC1α protein levels, which is associated with increased expression of thermogenic program. We conclude that Suv420h2 is a key regulator of brown/beige adipocyte development and thermogenesis.