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| Status |
Public on May 09, 2024 |
| Title |
The Histone Methyltransferase SUV420H2 Regulates Brown and Beige Adipocyte Thermogenesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Activation of brown adipose tissue (BAT) thermogenesis increases energy expenditure and alleviates obesity. Epigenetic regulation has emerged as a key mechanism underlying BAT development and function. To study the epigenetic regulation of BAT thermogenesis, we surveyed the expression of epigenetic enzymes that catalyze histone modifications in developmental beige adipocytes and found a unique expression pattern of suppressor of variegation 4-20 homolog 2 (Drosophila) (Suv420h2), a histone methyltransferase that preferentially catalyzes the tri-methylation at histone H4 lysine 20 (H4K20me3), a hallmark of gene silencing. Here we discovered that Suv420h2 expression parallels that of UCP1 expression 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 showed 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.
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| Overall design |
Subcutaneous white fat mRNA profiles of 12-week-old WT and H2KO as well as WT and AH2Tg mice after 7-day cold exposure
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| Contributor(s) |
Xue B, Shi H |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Oct 02, 2023 |
| Last update date |
May 10, 2024 |
| Contact name |
Bingzhong Xue |
| Organization name |
Georgia State University
|
| Department |
Biology
|
| Street address |
50 Decatur St. SE
|
| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30303 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1023212 |
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