| Liver-enriched inhibitory protein (LIP) actively inhibits preadipocyte differentiation through histone deacetylase 1 (HDAC1). | |
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MedLine Citation:
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PMID: 21521687 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The CCAAT/enhancer-binding protein β (C/EBPβ) is expressed as three isoforms (LAP*, liver-enriched activating protein (LAP), and liver-enriched inhibitory protein (LIP)) that differentially regulate gene expression. The interplay between LAP*, LAP, and LIP in regulating cellular processes is largely unknown, and LIP has been largely regarded to repress transcription through a passive heterodimerization-dependent mechanism. Recently, we have shown that p300/GCN5 and mSin3A/HDAC1 differentially regulate the ability of C/EBPβ to stimulate preadipocyte differentiation through activation of C/ebpα transcription. Here, we have mapped requirements for binding of mSin3A/HDAC1 to LAP/LAP* and LIP to a 4-amino acid motif in the central region of LAP/LAP* (residues 153-156) and the N terminus of LIP. Reducing mSin3A/HDAC1 binding to LAP/LAP* and LIP through deletion of this motif reduced the recruitment of HDAC1 to the C/ebpα promoter and increased preadipocyte differentiation stimulated by insulin and 1-methyl-3-isobutylxanthine. Additional studies showed that the interaction of HDAC1 with LIP provides for active repression of C/ebpα transcription and is largely responsible for the ability of LIP and HDAC1 to repress preadipocyte differentiation. Thus, although mSin3A/HDAC1 interacted readily with LAP/LAP* in addition to LIP and that expression of LAP/LAP* was sufficient to recruit HDAC1 to the C/ebpα promoter, mutations in C/ebpβ that abrogated HDAC1 association to LAP/LAP* in the absence of LIP provided no additional stimulation of differentiation or transcription beyond the deletion of LIP alone. The implication of these results for the interaction between p300/GCN5 and mSin3A/HDAC1 in regulating C/EBPα transcription and preadipocyte differentiation are discussed. |
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Authors:
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Houssein-Salem Abdou; Ella Atlas; Robert J G Haché |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-04-25 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 286 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-06-13 Completed Date: 2011-08-30 Revised Date: 2012-09-24 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 21488-99 Citation Subset: IM |
Affiliation:
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Graduate Program in Biochemistry, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adipocytes
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cytology* Animals CCAAT-Enhancer-Binding Protein-beta / genetics* COS Cells Cell Differentiation Cercopithecus aethiops Dimerization Gene Deletion Gene Expression Regulation* Mice Mutation NIH 3T3 Cells Promoter Regions, Genetic Protein Binding Transcription, Genetic |
| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/CCAAT-Enhancer-Binding Protein-beta |
| Comments/Corrections | |
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