The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
EHMT1 controls brown adipose cell fate and thermogenesis through the PRDM16 complex
Open accessAbstract
Brown adipose tissue (BAT) dissipates chemical energy in the form of heat as a defence against hypothermia and obesity. Current evidence indicates that brown adipocytes arise from Myf5+ dermotomal precursors through the action of PR domain containing protein 16 (PRDM16) transcriptional complex. However, the enzymatic component of the molecular switch that determines lineage specification of brown adipocytes remains unknown. Here we show that euchromatic histone-lysine N-methyltransferase 1 (EHMT1) is an essential BAT-enriched lysine methyltransferase in the PRDM16 transcriptional complex and controls brown adipose cell fate. Loss of EHMT1 in brown adipocytes causes a severe loss of brown fat characteristics and induces muscle differentiation in vivo through demethylation of histone 3 lysine 9 (H3K9me2 and 3) of the muscle-selective gene promoters. Conversely, EHMT1 expression positively regulates the BAT-selective thermogenic program by stabilizing the PRDM16 protein. Notably, adipose-specific deletion of EHMT1 leads to a marked reduction of BAT-mediated adaptive thermogenesis, obesity and systemic insulin resistance. These data indicate that EHMT1 is an essential enzymatic switch that controls brown adipose cell fate and energy homeostasis.
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Cites
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Cold-Activated Brown Adipose Tissue in Healthy Men
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Functional Brown Adipose Tissue in Healthy Adults
Virtanen, K. A., Lidell, M. E., Orava, J., Heglind, M., Westergren, R., Niemi, T., Taittonen, M., Laine, J., Savisto, N.-J., Enerbäck, S., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808949 · Cited by 3,058
PRDM16 controls a brown fat/skeletal muscle switch
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Self-citationHigh Incidence of Metabolically Active Brown Adipose Tissue in Healthy Adult Humans
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Initiation of myoblast to brown fat switch by a PRDM16–C/EBP-β transcriptional complex
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Self-citationNonshivering thermogenesis and its adequate measurement in metabolic studies
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Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex
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Self-citationβ-catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse
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Cited by
Brown and beige fat: Molecular parts of a thermogenic machine
Cohen, P., & Spiegelman, B. M. (2015) · Diabetes · doi:10.2337/db15-0318 · Cited by 259
Jiang, N., Yang, M., Han, Y., Zhao, H., & Sun, L. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.870250 · Cited by 68
Metadata
- Authors
- Ohno, H., Shinoda, K., Ohyama, K., Sharp, L. Z., & Kajimura, S.
- Venue
- Nature
- Published
- 2013-11-06
- Volume
- 504
- Issue
- 7478
- Pages
- 163-167
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2063020711
- Cited by
- 329
- References
- 13
- FWCI
- 18.97
- Type
- journal article
- Language
- en
- Open access
- green
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- Ohno, H., Shinoda, K., Ohyama, K., Sharp, L. Z., & Kajimura, S. (2013). EHMT1 controls brown adipose cell fate and thermogenesis through the PRDM16 complex. Nature. https://doi.org/10.1038/nature12652
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