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Brown adipocytes oxidize fatty acids to produce heat in response to cold or to excessive energy intake; stimulation of brown fat development and function may thus counteract obesity. Brown adipogenesis requires activation of the transcription factor C/EBPβ and recruitment of the zinc finger protein Prdm16, but upstream inducers of these proteins are incompletely defined. Here, we show that genetic inactivation of Plac8, a gene encoding an evolutionarily conserved protein, induces cold intolerance, and late-onset obesity, as well as abnormal morphology and impaired function of brown adipocytes. Using brown preadipocyte lines we show that Plac8 is required for brown fat differentiation, that its overexpression induces C/EBPβ and Prdm16, and that upon induction of differentiation Plac8 associates with C/EBPβ and binds to the C/EBPβ promoter to induce its transcription. Thus, Plac8 is a critical upstream regulator of brown fat differentiation and function that acts, at least in part, by inducing C/EBPβ expression.
Pubmed ID: 21982742
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TESS is a web tool for predicting transcription factor binding sites in DNA sequences. It can identify binding sites using site or consensus strings and positional weight matrices from the TRANSFAC, JASPAR, IMD, and our CBIL-GibbsMat database. You can use TESS to search a few of your own sequences or for user-defined CRMs genome-wide near genes throughout genomes of interest. Search for CRMs Genome-wide: TESS now has the ability to search whole genomes for user defined CRMs. Try a search in the AnGEL CRM Searches section of the navigation bar.. You can search for combinations of consensus site sequences and/or PWMs from TRANSFAC or JASPAR. Search DNA for Binding Sites: TESS also lets you search through your own sequence for TFBS. You can include your own site or consensus strings and/or weight matrices in the search. Use the Combined Search under ''Site Searches'' in the menu or use the box for a quick search. TESS assigns a TESS job number to all sequence search jobs. The job results are stored on our server for a period of time specified in the search submit form. During this time you may recall the search results using the form on this page. TESS can also email results to you as a tab-delimited file suitable for loading into a spreadsheet program. Query for Transcription Factor Info: TESS also has data browsing and querying capabilities to help you learn about the factors that were predicted to bind to your sequence. Use the Query TRANSFAC or Query Matrices links above or use the search interface provided from the home page.
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