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

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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.