The role of nuclear factor NF-Y/CP1 in the transcriptional regulation of the human aldehyde dehydrogenase 2-encoding gene

Gene
M J StewartD W Crabb

Abstract

Mitochondrial aldehyde dehydrogenase (ALDH2) activity is produced at low levels in many tissues, with highest production in liver. Transfection assays using the first 600 bp of upstream DNA provided evidence for both positive and negative regulatory elements in the proximal promoter. A region from -79 to -116 bp was protected in DNase I footprinting assays and bound in electrophoretic mobility shift assays (EMSA) by a nuclear factor found in all cell lines and tissues tested. This region, denoted FP160, contained the consensus recognition sites for Sp1 and AP2, and a CCAAT box. The CCAAT box was specifically protected by a nuclear factor in methylation interference assays. Mutagenesis of specific bp within the CCAAT box eliminated protein binding in vitro and decreased transcriptional activity from the ALDH2 promoter approximately 50% in reporter gene assays. Competition experiments showed that the nuclear factor binding to the FP160 oligodeoxyribonucleotide (oligo) was competed by oligos corresponding to an NY-Y/CP1-binding site to a greater extent than by those containing sites for CTF/NF1, C/EPB or CP2. The heat stability, resistance to proteinase K digestion, sensitivity to inhibition of DNA binding by o-phenanthroline, and...Continue Reading

References

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Citations

Aug 28, 2007·Alcohol Research & Health : the Journal of the National Institute on Alcohol Abuse and Alcoholism·Howard J Edenberg
Apr 4, 1998·Nucleic Acids Research·R Mantovani
Jul 9, 1999·Alcoholism, Clinical and Experimental Research·S HaradaM Tsutsumi
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Jun 8, 2001·Alcoholism, Clinical and Experimental Research·S HaradaS Higuchi
Jan 16, 2009·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·Yukiko KimuraKiyofumi Saijoh
Mar 22, 2003·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Jens-Christian KrögerMatthias Löhr
Dec 9, 2000·Molecular Biology and Evolution·K K KoretkeJ R Brown
Oct 13, 2000·Molecular Microbiology·M B Yarmolinsky
Apr 5, 2003·Molecular Microbiology·Marat SadykovIchizo Kobayashi
Apr 2, 2008·Molecular and Cellular Biology·Thomas PavelitzAlan M Weiner
Apr 21, 2006·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·Mitsuru KimuraSusumu Higuchi
Apr 22, 2017·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·Hansi PathakMathias Rhein

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