國家衛生研究院 NHRI:Item 3990099045/2303
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    题名: Distant HNF1 site as a master control for the human class 1 alcohol dehydrogenase gene expression
    作者: Su, JS;Tsai, TF;Chang, HM;Chao, KM;Su, TS;Tsai, SF
    贡献者: Division of Molecular and Genomic Medicine
    摘要: Gene duplication and divergence have contributed to the biochemical diversity of the alcohol dehydrogenase (ADH) family. Class I ADH is the major enzyme that catalyzes alcohol to acetaldehyde in the liver. To investigate the mechanism(s) controlling tissue-specific and temporal regulation of the three human class I ADH genes (ADH1A, ADH1B, and ADH1C), we compared genomic sequences for the human and mouse ADH loci and analyzed human ADH gene expression in BAC transgenic mice carrying different lengths of the upstream sequences of the class I ADH. A conserved noncoding sequence, located between the class I and class IV ADH (ADH7) genes, was found to be essential for directing class I ADH gene expression in fetal and adult livers. Within this region, a 275-bp fragment displaying liver-specific DNase I hypersensitivity was bound by HNF1. The HNF1-containing upstream sequence enhanced all three class I ADH promoters in an orientation-dependent manner, and the transcriptional activation depended on binding to the HNF1 site. Deletion of the conserved HNF1 site in the BAC led to the shutdown of human class I ADH gene expression in the transgenic livers, leaving ADH1C gene expression in the stomach unchanged. Moreover, interaction between the upstream element and the class I ADH gene promoters was demonstrated by chromosome conformation capture, suggesting a DNA looping mechanism is involved in gene activation. Taken together, our data indicate that HNF1 binding, at similar to 51 kb upstream, plays a master role in controlling human class I ADH gene expression and may govern alcohol metabolism in the liver.
    关键词: Biochemistry & Molecular Biology
    日期: 2006-07-21
    關聯: Journal of Biological Chemistry. 2006 Jul;281(29):19809-19821.
    Link to: http://dx.doi.org/10.1074/jbc.M603638200
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1083-351X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000239038200004
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33746002959
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