The apolipoprotein CIII enhancer regulates both extensive histone modification and intergenic transcription of human apolipoprotein AI/CIII/AIV genes but not apolipoprotein AV.
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.
Li
Ya-Jun
YJ
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005 China.
Wei
Yu-Sheng
YS
Fu
Xiang-Hui
XH
Hao
De-Long
DL
Xue
Zheng
Z
Gong
Huan
H
Zhang
Zhu-Qin
ZQ
Liu
De-Pei
DP
Liang
Chih-Chuan
CC
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
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