The orphan nuclear receptor Rev-erbbeta recruits Tip60 and HDAC1 to regulate apolipoprotein CIII promoter.

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.