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

Abstract 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-erbα and Rev-erbβ, are members of the nuclear receptor superfamily and act as transcriptional repressors. In this study, the role of recruitment of co-factors by Rev-erbβ and acetylation of Rev-erbβ in modulating apolipoprotein CIII ( apoCIII ) transcription were investigated. Rev-erbβ 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-erbβ and recruited to the apoCIII promoter by Rev-erbβ. Tip60 was able to acetylate Rev-erbβ and relieve the apoCIII repression mediated by Rev-erbβ. This de-repression effect depended on acetylation of Rev-erbβ at its RXKK motif by Tip60. In addition, histone deacetylase 1 (HDAC1) interacted with Rev-erbβ and was recruited to the apoCIII promoter by Rev-erbβ to antagonize Tip60's activity. Taken together, we have provided evidence that Rev-erbβ modulates the apoCIII gene expression by recruiting different transcription co-activator or co-repressor.