| First Author | Abdou HS | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 24 | Pages | 21488-99 |
| PubMed ID | 21521687 | Mgi Jnum | J:173645 |
| Mgi Id | MGI:5049833 | Doi | 10.1074/jbc.M110.211540 |
| Citation | Abdou HS, et al. (2011) Liver-enriched Inhibitory Protein (LIP) Actively Inhibits Preadipocyte Differentiation through Histone Deacetylase 1 (HDAC1). J Biol Chem 286(24):21488-99 |
| abstractText | The CCAAT/enhancer-binding protein beta (C/EBPbeta) 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/EBPbeta to stimulate preadipocyte differentiation through activation of C/ebpalpha 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/ebpalpha 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/ebpalpha 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/ebpalpha promoter, mutations in C/ebpbeta 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/EBPalpha transcription and preadipocyte differentiation are discussed. |
