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

Luke O. Dannenberg, Hui Ju Chen, Howard Edenberg

Research output: Contribution to journalArticle

12 Citations (Scopus)

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

Fingerprint

Hepatocyte Nuclear Factors
Alcohol Dehydrogenase
Genes
Organ Specificity
Electrophoretic Mobility Shift Assay

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

GATA-2 and HNF-3β regulate the human alcohol dehydrogenase 1A (ADH1A) gene. / Dannenberg, Luke O.; Chen, Hui Ju; Edenberg, Howard.

In: DNA and Cell Biology, Vol. 24, No. 9, 09.2005, p. 543-552.

Research output: Contribution to journalArticle

Dannenberg, Luke O. ; Chen, Hui Ju ; Edenberg, Howard. / GATA-2 and HNF-3β regulate the human alcohol dehydrogenase 1A (ADH1A) gene. In: DNA and Cell Biology. 2005 ; Vol. 24, No. 9. pp. 543-552.
@article{00de45d132f64fe48d76a8c9618a8e52,
title = "GATA-2 and HNF-3β regulate the human alcohol dehydrogenase 1A (ADH1A) gene",
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.",
author = "Dannenberg, {Luke O.} and Chen, {Hui Ju} and Howard Edenberg",
year = "2005",
month = "9",
doi = "10.1089/dna.2005.24.543",
language = "English",
volume = "24",
pages = "543--552",
journal = "DNA and Cell Biology",
issn = "1044-5498",
publisher = "Mary Ann Liebert Inc.",
number = "9",

}

TY - JOUR

T1 - GATA-2 and HNF-3β regulate the human alcohol dehydrogenase 1A (ADH1A) gene

AU - Dannenberg, Luke O.

AU - Chen, Hui Ju

AU - Edenberg, Howard

PY - 2005/9

Y1 - 2005/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=25144442698&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=25144442698&partnerID=8YFLogxK

U2 - 10.1089/dna.2005.24.543

DO - 10.1089/dna.2005.24.543

M3 - Article

C2 - 16153155

AN - SCOPUS:25144442698

VL - 24

SP - 543

EP - 552

JO - DNA and Cell Biology

JF - DNA and Cell Biology

SN - 1044-5498

IS - 9

ER -