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标题：HNF4 and COUP-TFII interact to modulate transcription of the cholesterol 7α-hydroxylase gene (CYP7A1)
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作者：Diane Stroup ; John Y. L. Chiang
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2000
卷号：41
期号：1
页码：1-11
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：The gene for cholesterol 7α-hydroxylase ( CYP7A1 ) contains a sequence at nt −149 to −118 that was found to play a large role in determining the overall transcriptional activity and regulation of the promoter. Hepatocyte nuclear factor 4 (HNF4) and chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) synergistically activate transcription of the CYP7A1 promoter. Transactivation of CYP7A1 by HNF4 in the human hepatoma cell line, HepG2, was enhanced by cotransfection with COUP-TFII or the basal transcription element binding protein (BTEB). HNF4 prepared from rat liver nuclear extracts bound to oligomers homologous to the nt −146 to −134 sequences in electrophoretic mobility shift assays (EMSA), which corresponded to a conserved region containing a direct repeat of hormone response elements spaced by one nucleotide (DR1). The sequences surrounding this DR1 were found to be essential for the HNF4 transactivation. In vitro-translated COUP-TFII was found to bind the adjacent sequences from nt −139 to −128 (DR0), but COUP-TFII interacted with this region at a much lower affinity than to the COUP-TFII-site at nt −72 to −57 (DR4). Mutations at nt −139 to −128 or nt −72 to −57 reduced the COUP-TFII and HNF4 synergy; however, these COUP-TFII-binding sequences were not absolutely required for the cooperative effect of HNF4 and COUP-TFII on transactivation. These results indicated that the observed transactivation was the result of protein/protein interactions facilitated by the juxtaposition of the binding elements. —Stroup, D., and J. Y. L. Chiang. HNF4 and COUP-TFII interact to modulate transcription of the cholesterol 7α-hydroxylase gene ( CYP7A1 ). J. Lipid Res. 2000. 41: 1–11.
关键词：bile acid synthesis ; hepatocyte nuclear factor 4 ; chicken ovalbumin upstream promoter transcription factor II ; orphan receptors ; transcriptional regulation ; cholesterol metabolism