Document Detail


Liver-enriched inhibitory protein (LIP) actively inhibits preadipocyte differentiation through histone deacetylase 1 (HDAC1).
MedLine Citation:
PMID:  21521687     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Houssein-Salem Abdou; Ella Atlas; Robert J G Haché
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-04-25
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-13     Completed Date:  2011-08-30     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  21488-99     Citation Subset:  IM    
Affiliation:
Graduate Program in Biochemistry, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adipocytes / 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:
//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Protein-beta
Comments/Corrections

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