title: The orphan nuclear receptor Rev-erbbeta 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-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.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai 200433, China.
authors.forename: Jiadong
authors.initials: J
authors.lastname: Wang
authors.forename: Nansong
authors.initials: N
authors.lastname: Liu
authors.forename: Zhongle
authors.initials: Z
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Chi
authors.initials: C
authors.lastname: Song
authors.forename: Hanying
authors.initials: H
authors.lastname: Yuan
authors.forename: Yu-Yang
authors.initials: YY
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D053305:Apolipoprotein C-III / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases / Q000378:metabolism*; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism*; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D013347:Subcellular Fractions; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D053305:Apolipoprotein C-III; C090977:NR1D2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases