Molecular anatomy of the human glucose 6‐phosphate dehydrogenase core promoter

Abstract

The gene encoding glucose 6-phosphate dehydrogenase (G6PD), which plays a pivotal role in cell defense against oxidative stress, is ubiquitously expressed at widely different levels in various tissues; moreover, G6PD expression is regulated by a number of stimuli. In this study we have analyzed the molecular anatomy of the G6PD core promoter. Our results indicate that the G6PD promoter is more complex than previously assumed; G6PD expression is under the control of several elements that are all required for correct promoter functioning and, furthermore, a still unidentified mammalian specific factor is needed.z 1998 Federation of European Biochemical Societies.

Nuclease-hypersensitive Chromatin Formed by a CpG Island in Human DNA Cloned as an Artificial Chromosome in Yeast

“…The positioning extends into the transcriptional unit, about 1 kb beyond the limits of the CpG island. This may suggest that this region contributes to the chromatin organization of the G6PD gene in human cells and to the control of its expression (12).…”

“…It carries the 3Ј part of the gene coding for G6PD including the first two exons as well as the accompanying CpG island. A DNA segment extracted from the island (nucleotide 2528 -2654 from the beginning of the insert) was capable of acting as a core promoter, assuring the regulation of expression of a reporter gene in mammalian but not in Drosophila cells (12). The full nucleotide genomic sequence of the region is available from GenBank™ (Locus HUMFLNG6PD).…”

Transcriptional and epigenetic basis for restoration of G6PD enzymatic activity in human G6PD-deficient cells

“…Of these, Motifs 3 and 4 had been shown previously to be part of the essential core promoter 24 and had been validated as bona fide Sp1 binding sites in vitro. 25 To dissect the role of cis DNA elements in G6PD transcription, we first carried out a promoter deletion analysis. In both the absence and the presence of NaBu, G6PD promoter activity depended on a proximal 562-bp promoter fragment containing 7 GC-rich motifs, Figure 1.…”

Oxidative Stress: Cause and Consequence of Diseases

“…Enhanced activity of G6PDH, a lipogenic enzyme, was found at diabetes and obesity (Gupte, 2010). In humans, G6PDH is regulated by many transcription factors, in particular, SREBP-1a (sterol regulatory element binding protein) (Amemiya-Kudo et al, 2002), AP-1 (Kletzien et al, 1994) and Sp1 (Franzè et al, 1998). It was shown that elevation of G6PDH activity might lead to enhanced lipid synthesis (Salati et al, 2001;Park et al, 2005;Lee et al, 2011) and to possible reductive stress (Dimmeler & Zeiher, 2007;Rajasekaran et al, 2007;Ralser & Benjamin, 2008).…”