EBF2 determines and maintains brown adipocyte identity
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE43763 | GEO | 2013/03/18
SECONDARY ACCESSION(S): PRJNA187365
REPOSITORIES: GEO
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Project description:The master transcription factor Ppar? regulates the general differentiation program of both brown and white adipocytes. However, it has been unclear whether Ppar? also controls fat lineage-specific characteristics. Here, we show that early B cell factor-2 (Ebf2) regulates Ppar? binding activity to determine brown versus white adipocyte identity. The Ebf DNA-binding motif was highly enriched within brown adipose-specific Ppar? binding sites that we identified by genome-wide ChIP-Seq. Of the Ebf isoforms, Ebf2 was selectively expressed in brown relative to white adipocytes and was bound at brown adipose-specific Ppar? target genes. When expressed in myoblasts or white preadipose cells, Ebf2 recruited Ppar? to its brown-selective binding sites and reprogrammed cells to a brown fat fate. Brown adipose cells and tissue from Ebf2-deficient mice displayed a loss of brown-specific characteristics and thermogenic capacity. Together, these results identify Ebf2 as a key transcriptional regulator of brown fat cell fate and function.
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Project description:EBF2 activates the expression of brown fat-selective genes in adipocytes, but whether EBF2 regulates these genes via direct binding was unknown. To address this question, we analyzed the genome-wide binding profile of EBF2 in BAT using chromatin immunoprecipitation followed by deep sequencing (ChIP-seq). To determine if EBF2 is required for the activity of lineage-specific enhancers, we examined the levels of PPARγ, RNA Polymerase II (Pol II), and H3K27ac at brown fat-specific genes in wildtype (WT) and Ebf2 KO BAT.
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