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|Title:||SHARP1/DEC2 inhibits adipogenic differentiation by regulating the activity of C/EBP||Authors:||Gulbagci, N.T.
|Issue Date:||2009||Citation:||Gulbagci, N.T., Li, L., Ling, B., Gopinadhan, S., Walsh, M., Rossner, M., Nave, K.-A., Taneja, R. (2009). SHARP1/DEC2 inhibits adipogenic differentiation by regulating the activity of C/EBP. EMBO Reports 10 (1) : 79-86. ScholarBank@NUS Repository. https://doi.org/10.1038/embor.2008.207||Abstract:||SHARP1, a basic helix-loop-helix transcription factor, is expressed in many cell types; however, the mechanisms by which it regulates cellular differentiation remain largely unknown. Here, we show that SHARP1 negatively regulates adipogenesis. Although expression of the early marker CCAAT/enhancer binding protein β (C/EBPβ) is not altered, its crucial downstream targets C/EBPα and peroxisome proliferator-activated receptor γ (PPARγ) are downregulated by SHARP1. Protein interaction studies confirm that SHARP1 interacts with and inhibits the transcriptional activity of both C/EBPβ and C/EBPα, and enhances the association of C/EBPβ with histone deacetylase 1 (HDAC1). Consistently, in SHARP1-expressing cells, HDAC1 and the histone methyltransferase G9a are retained at the C/EBP regulatory sites on the C/EBPα and PPARγ2 promoters during differentiation, resulting in inhibition of their expression. Interestingly, treatment with troglitazone results in displacement of HDAC1 and G9a, and rescues the differentiation defect of SHARP1-overexpressing cells. Our data indicate that SHARP1 inhibits adipogenesis through the regulation of C/EBP activity, which is essential for PPARγ-ligand-dependent displacement of co-repressors from adipogenic promoters.||Source Title:||EMBO Reports||URI:||http://scholarbank.nus.edu.sg/handle/10635/107458||ISSN:||1469221X||DOI:||10.1038/embor.2008.207|
|Appears in Collections:||Staff Publications|
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