title: The apolipoprotein CIII enhancer regulates both extensive histone modification and intergenic transcription of human apolipoprotein AI/CIII/AIV genes but not apolipoprotein AV.
abstract: The apolipoprotein (apo) AI/CIII/AIV/AV cluster genes are expressed at different levels in the liver and intestine. The apoCIII enhancer, a common regulatory element, regulates the tissue-specific expression of apoAI, apoCIII, and apoAIV but not apoAV. To study this regulation at the chromatin level, the histone modifications and intergenic transcription in the human apoAI/CIII/AIV/AV cluster were investigated in HepG2 and Caco-2 cells and in the livers of transgenic mice carrying the human gene cluster constructs with or without the apoCIII enhancer. We found that both the promoters and the intergenic regions of the apoAI/CIII/AIV genes were hyperacetylated and formed an open subdomain that did not include the apoAV gene. Hepatic and intestinal intergenic transcripts were identified to transcribe bidirectionally with strand preferences along the cluster. The deletion of the apoCIII enhancer influenced both histone modification and intergenic transcription in the apoAI/CIII/AIV gene region. These results demonstrate that the apoCIII enhancer contributes to the maintenance of an active chromatin subdomain of the apoAI/CIII/AIV genes, but not apoAV.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005 China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Li
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Wei
authors.forename: Xiang-Hui
authors.initials: XH
authors.lastname: Fu
authors.forename: De-Long
authors.initials: DL
authors.lastname: Hao
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xue
authors.forename: Huan
authors.initials: H
authors.lastname: Gong
authors.forename: Zhu-Qin
authors.initials: ZQ
authors.lastname: Zhang
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Liu
authors.forename: Chih-Chuan
authors.initials: CC
authors.lastname: Liang
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000737:chemistry; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology*; D001054:Apolipoproteins A / Q000096:biosynthesis* / Q000737:chemistry; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D008957:Models, Genetic; D005810:Multigene Family
chemical_list: C437704:APOA5 protein, human; D016632:Apolipoprotein A-I; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D006657:Histones; C022205:apolipoprotein A-IV