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Brown fat can reduce obesity through the dissipation of calories as heat. Control of thermogenic gene expression occurs via the induction of various coactivators, most notably PGC-1α. In contrast, the transcription factor partner(s) of these cofactors are poorly described. Here, we identify interferon regulatory factor 4 (IRF4) as a dominant transcriptional effector of thermogenesis. IRF4 is induced by cold and cAMP in adipocytes and is sufficient to promote increased thermogenic gene expression, energy expenditure, and cold tolerance. Conversely, knockout of IRF4 in UCP1(+) cells causes reduced thermogenic gene expression and energy expenditure, obesity, and cold intolerance. IRF4 also induces the expression of PGC-1α and PRDM16 and interacts with PGC-1α, driving Ucp1 expression. Finally, cold, β-agonists, or forced expression of PGC-1α are unable to cause thermogenic gene expression in the absence of IRF4. These studies establish IRF4 as a transcriptional driver of a program of thermogenic gene expression and energy expenditure.
Pubmed ID: 24995979 RIS Download
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An extensible and customizable gene annotation portal that emphasizes community extensibility and user customizability. It is a complete resource for learning about gene and protein function. Community extensibility reflects a belief that any BioGPS user should be able to add new content to BioGPS using the simple plugin interface, completely independently of the core developer team. User customizability recognizes that not all users are interested in the same set of gene annotation data, so the gene report layouts enable each user to define the information that is most relevant to them. Currently, BioGPS supports eight species: Human (Homo sapiens), Mouse (Mus musculus), Rat (Rattus norvegicus), Fruitfly (Drosophila melanogaster), Nematode (Caenorhabditis elegans), Zebrafish (Danio rerio), Thale-cress (Arabidopsis thaliana), Frog (Xenopus tropicalis), and Pig (Sus scrofa). BioGPS presents data in an ortholog-centric format, which allows users to display mouse plugins next to human ones. Our data for defining orthologs comes from NCBI's HomoloGene database.
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