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The orphan receptors, Rev-erba and Rev-erbb, are members of the nuclear receptor superfamily and specifically repress apolipoprotein CIII (apoCIII) gene expression in rats and humans. Moreover, Rev-erbanull mutant mice have elevated very low density lipoprotein triacylglycerol and apoCIII levels. | ễFEBS Journal A zinc finger HIT domain-containing protein ZNHIT-1 interacts with orphan nuclear hormone receptor Rev-erbb and removes Rev-erbp-induced inhibition of apoCIII transcription Jiadong Wang1 Yang Li1 Min Zhang1 Zhongle Liu1 Cong Wu1 Hanying Yuan1 Yu-Yang Li1 Xin Zhao2 and Hong Lu1 1 State Key Laboratory of Genetic Engineering Schoolof Life Sciences Fudan University Shanghai China 2 Department of AnimalScience McGillUniversity Montreal Canada Keywords apoCIII Rev-erbb transcriptionalregulation zinc finger HIT domain-containing protein 1 ZNHIT-1 Correspondence H. Lu State Key Laboratory of Genetic Engineering School of Life Sciences Fudan University Shanghai 200433 China Fax 86 21 65642505 Tel 86 21 65642505 E-mail honglu0211@yahoo.com Received 27 June 2007 revised 15 August 2007 accepted 22 August 2007 doi 10.1111 j.1742-4658.2007.06062.x The orphan receptors Rev-erba and Rev-erbp are members of the nuclear receptor superfamily and specifically repress apolipoprotein CIII apoCIII gene expression in rats and humans. Moreover Rev-erba null mutant mice have elevated very low density lipoprotein triacylglycerol and apoCIII levels. However ligands for Rev-erb are unknown and the regulatory mechanism of Rev-erb is poorly understood. Conceivably cofactors for Rev-erb may play an important role in the regulation of lipid metabolism. In this study a zinc finger HIT domain-containing protein ZNHIT-1 interacted with Rev-erbp. ZNHIT-1 was found to be a conserved protein in eukaryotes and was highly abundant in human liver. Furthermore ZNHIT-1 was identified as a nuclear protein. Serial truncated fragments and substitution mutations established a putative nuclear localization signal at amino acids 38-47 of ZNHIT-1. A putative ligandbinding domain of Rev-erbp and the FxxLL motif of ZNHIT-1 were required for their interaction. Finally ZNHIT-1 was recruited by Rev-erbb to the apoCIII promoter and removed the Rev-erbb-induced inhibition of apoCIII transcription. These .