{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T05:55:32Z","timestamp":1715406932830},"reference-count":49,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2000,8,1]]},"abstract":"<jats:p>The divergent homeobox gene Hex is expressed in both developing and mature liver. A putative Hex binding site was identified in the promoter region of the liver-specific Na<jats:sup>+<\/jats:sup>-bile acid cotransporter gene ( ntcp), and we hypothesized that Hex regulates the ntcp promoter through this site. Successive 5\u2032-deletions of the ntcp promoter in a luciferase reporter construct transfected into Hep G2 cells confirmed a Hex response element (HRE) within the ntcppromoter (nt \u2212733\/\u2212714). Moreover, p-CMHex transactivated a heterologous promoter construct containing HRE multimers (p4xHRELUC), whereas a 5-bp mutation of the core HRE eliminated transactivation. A dominant negative form of Hex (p- Hex-DN) suppressed basal luciferase activity of p-4xHRELUC and inhibited activation of this construct by p-CMHex. Interestingly, p-CMHex transactivated the HRE in Hep G2 cells but not in fibroblast-derived COS cells, suggesting the possibility that Hex protein requires an additional liver cell-specific factor(s) for full activity. Electrophoretic mobility shift assays confirmed that liver and Hep G2 cells contain a specific nuclear protein that binds the native HRE. We have demonstrated that the liver-specific ntcp gene promoter is the first known target of Hex and is a useful tool for evaluating function of the Hex protein.<\/jats:p>","DOI":"10.1152\/ajpgi.2000.279.2.g347","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T15:26:08Z","timestamp":1514129168000},"page":"G347-G355","source":"Crossref","is-referenced-by-count":39,"title":["Divergent homeobox gene<i>Hex<\/i>regulates promoter of the Na<sup>+<\/sup>-dependent bile acid cotransporter"],"prefix":"10.1152","volume":"279","author":[{"given":"Lee A.","family":"Denson","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Yale University, New Haven, Connecticut 06520-8064"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saul J.","family":"Karpen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yale University, New Haven, Connecticut 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