GATA-2 and HNF-3β regulate the human alcohol dehydrogenase 1A (ADH1A) gene

Luke O. Dannenberg, Hui Ju Chen, Howard J. Edenberg

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

In this paper, we have identified several distal cis-acting elements that contribute to the regulation and tissue-specificity of ADH1A, which encodes an alcohol dehydrogenase (ADH) that metabolizes ethanol. A negative element from bp -1873 to -1558, relative to the translational start site, decreased transcriptional activity to 52% in H4IIE-C3 cells and 70% in CV-1 cells. A positive element from bp -2459 to -2173 increased transcriptional activity twofold in H4IIE-C3 cells and 1.7-fold in CV-1 cells. Gel mobility shift and supershift assays demonstrated that GATA-2 bound a region within this positive element. A tissue-specific regulatory element from bp -6380 to -5403 increased transcription twofold in H4IIE-C3 cells while decreasing transcription to 86% in CV-1 cells. Within this tissue-specific fragment, the region from bp -5668 to -5403 increased transcription 1.7-fold in H4IIE-C3 cells and 1.3-fold in CV-1 cells. Hepatocyte nuclear factor-3β (HNF-3β) bound a region of the tissue-specific element in CV-1 cells, but not in H4IIE-C3 cells. Positive regulation of the ADH1A gene may be influenced by GATA-2 binding, while differences in HNF-3β binding in cells/tissues may contribute to tissue specificity.

Original languageEnglish (US)
Pages (from-to)543-552
Number of pages10
JournalDNA and Cell Biology
Volume24
Issue number9
DOIs
StatePublished - Sep 1 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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