The orphan nuclear receptor Rev-erbβ 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-erb alpha and Rev-erb beta, are members of the nuclear receptor superfamily and act as transcriptional repressors. In this study, the role of recruitment of co-factors by Rev-erb beta and acetylation of Rev-erb beta in modulating apolipoprotein CIII (apoCIII) transcription were investigated. Rev-erb beta 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-erb beta and recruited to the apoCIII promoter by Rev-erb beta. Tip60 was able to acetylate Rev-erb beta and relieve the apoCIII repression mediated by Rev-erb beta. This de-repression effect depended on acetylation of Rev-erb beta at its RXKK motif by Tip60. In addition, histone deacetylase 1 (HDAC1) interacted with Rev-erb beta and was recruited to the apoCIII promoter by Rev-erb beta to antagonize Tip60's activity. Taken together, we have provided evidence that Rev-erb beta modulates the apoCIII gene expression by recruiting different transcription co-activator or co-repressor. (C) 2007 Elsevier B.V. All rights reserved.