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Wang, J, Liu, N, Liu, Z, Li, Y, Song, C, Yuan, H, Li, YY, Zhao, X and Lu, H (2008) The orphan nuclear receptor Rev-erbbeta recruits Tip60 and HDAC1 to regulate apolipoprotein CIII promoter. Biochim. Biophys. Acta 1783:224-36

Nuclear hormone receptors function as ligand activated transcription factors. Ligand binding and modification such as acetylation have been reported to regulate nuclear hormone receptors. The orphan receptors, Rev-erbalpha and Rev-erbbeta, are members of the nuclear receptor superfamily and act as transcriptional repressors. In this study, the role of recruitment of co-factors by Rev-erbbeta and acetylation of Rev-erbbeta in modulating apolipoprotein CIII (apoCIII) transcription were investigated. Rev-erbbeta was found to transcriptionally repress apoCIII after binding to the apoCIII promoter. Tip60, a histone acetyl-transferase (HAT), was a novel binding partner for Rev-erbbeta and recruited to the apoCIII promoter by Rev-erbbeta. Tip60 was able to acetylate Rev-erbbeta and relieve the apoCIII repression mediated by Rev-erbbeta. This de-repression effect depended on acetylation of Rev-erbbeta at its RXKK motif by Tip60. In addition, histone deacetylase 1 (HDAC1) interacted with Rev-erbbeta and was recruited to the apoCIII promoter by Rev-erbbeta to antagonize Tip60's activity. Taken together, we have provided evidence that Rev-erbbeta modulates the apoCIII gene expression by recruiting different transcription co-activator or co-repressor.

PubMed Online version:10.1016/j.bbamcr.2007.09.004

Acetylation; Amino Acid Sequence; Apolipoprotein C-III/genetics; Base Sequence; Cell Line; Gene Expression Regulation; Histone Acetyltransferases/metabolism; Histone Deacetylase 1; Histone Deacetylases/metabolism; Humans; Molecular Sequence Data; Promoter Regions, Genetic/genetics; Protein Binding; Protein Interaction Mapping; Protein Transport; Receptors, Cytoplasmic and Nuclear/chemistry; Receptors, Cytoplasmic and Nuclear/metabolism; Repressor Proteins/chemistry; Repressor Proteins/metabolism; Subcellular Fractions; Transcription Factors/chemistry; Transcription Factors/metabolism; Transcription, Genetic