Variable numbers of pepsinogen genes are located in the centromeric region of human chromosome 11 and determine the high-frequency electrophoretic polymorphism.

Taggart, R T; Mohandas, T.; Shows, Thomas B.; Bell, G. I.

doi:10.1073/pnas.82.18.6240

Cited by 66 publications

(29 citation statements)

References 29 publications

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“…We chose this gene system as a model for the study of gastric-specific transcriptional regulation in mammalian cells, including man. Previous analyses (Taggart et al, 1985;Zelle et al, 1988) provided evidence that the human pepsinogen A genes are organized in haplotypes giving rise to polymorphic PGA isozymogen patterns. In contrast with the situation in man and monkey , Southern analyses of porcine genomic DNA suggest the presence of only a single PGA gene per haploid genome.…”

Section: Discussionmentioning

confidence: 99%

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Gastric chief cell‐specific transcription of the pepsinogen A gene

Meijerink¹,

Bebelman²,

Oldenburg³

et al. 1993

European Journal of Biochemistry

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The molecular mechanisms underlying the regulation of pepsinogen A (PGA) gene expression in mammalian cells are poorly understood. In this paper we describe the structural and functional analysis of the pepsinogen A gene promoter in the pig. By genomic Southern analyses we demonstrate that, in contrast with human PGA genes which are amplified and organized in haplotypes, only a single PGA gene is present per haploid porcine genome. With the aim of identifying promoter elements mediating the gastric mucosa cell-specific transcription of the PGA gene in pig, we isolated a PGA gene from a porcine genomic library. The nucleotide sequence of the first exon and 1.7 kb of the upstream DNA region were determined and compared with the corresponding regions of the human PGA gene encoding isozymogen Pg5. In order to study the promoter activity of the PGA gene a functional assay was developed: we succeeded in obtaining primary monolayer cultures of porcine gastric mucosal chief cells, suitable for transfection. Fragments of 5'-flanking and noncoding first exon sequences of the porcine and human PGA genes were linked to the chloramphenicol acetyltransferase (CAT) gene. The transcriptional activity of these hybrid genes was assessed in transient expression assays upon transfection (lipofection) of gastric and nongastric cells. Whereas PGA 5'-flanking sequences showed no promoter activity in nongastric cell types, the DNA region from -205 to +21 was found to be sufficient to direct expression of the porcine PGA constructs in a cell-specific manner. Further deletion analysis of the proximal promoter fragment identified several regions (-205 to -167, -127 to -67 and +2 to +21) acting synergistically in the transcriptional regulation of the PGA gene. In contrast, all human PGA-CAT constructs used failed to show promoter activity in porcine gastric chief cells, indicating species-specific control of PGA gene expression. In addition, the transcriptional activity of the porcine PGA promoter in chief cells from pig was completely abolished by in vitro CpG methylation. Footprint analyses of the proximal promoter fragment using nuclear extracts from either porcine gastric mucosal chief cells or liver revealed some notable differences between both extracts, which might reflect the interaction with (a) cell-specific factor(s).

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Section: Discussionmentioning

confidence: 99%

“…In man, PGA is encoded by a multigene family (Taggart et al, 1985;Zelle et al, 1988) located on chromosome llq12-13 (Zelle et al, 1985;Nakai et al, 1986). The PGA gene, comprising nine exons, encompasses approximately 9.4 kb of genomic DNA (Sogawa et al, 1983).…”

mentioning

confidence: 99%

Gastric chief cell‐specific transcription of the pepsinogen A gene

Meijerink¹,

Bebelman²,

Oldenburg³

et al. 1993

European Journal of Biochemistry

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“…The recipient yeast strain used in transformations was S. cerevisiae YM20 (MATa ura3-1 ura3-2 trpl-289 his3-532 ade2-l(ochre) galldell (8,(22)(23)(24)(25)(26). Total human genomic DNA was a gift of Margit Burnmeister (University of Michigan, Ann Arbor, MI).…”

Section: Methodsmentioning

confidence: 99%

Cloning of a human galactokinase gene (GK2) on chromosome 15 by complementation in yeast.

Lee¹,

Peterson²,

Calman³

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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A human cDNA encoding a galactokinase (EC 2.7.1.6) was isolated by complementation of a galactokinase-deficient (gal1-) strain of Saccharomyces cerevisiae. This cDNA encodes a predicted protein of 458 amino acids with 29% identity to galactokinase of Saccharomyces carlsbergensis. Previous studies have mapped a human galactokinase gene (GK1) to chromosome 17q23-25, closely linked to thymidine kinase. The galactokinase gene that we have isolated (GK2) is located on chromosome 15. The relationship between the disease locus for galactokinase deficiency galactosemia, which is responsible for cataracts in newborns and possibly presenile cataracts in adults, and the two galactokinase loci is unknown.

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“…PGs are synthesized as isozymogens which are divided into two groups, PGA and PGC, based on biochemical and immunological grounds [1,2]. At least three PGA genes are present in chromosome 11 [3,4] and one or more PGC gene(s) present in chromosome 6 [5,6], Four PGA (designated as PGA-2, 3, 4 and 5) and one or two PGC bands are usually detectable on agar or polyacrylamide gel electrophoresis.…”

Section: Introductionmentioning

confidence: 99%

Purification of recombinant human pepsinogens and their application as immunoassay standards

Aoki¹,

Tomaki²,

Satoh³

et al. 1998

IUBMB Life

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SUMMARYHuman pepsinogen (PG) A and C were cloned in Escherichia coli, but the levels of expression were low and unstable. When these were fused to maltose-binding protein (MBP), the fusion proteins (MBP-PGA and MBP-PGC) were expressed as the major products. Although these fused products were almost totally recovered from the insoluble fraction, the renaturation and purification procedures were easy and simple. MBP-PGA and the PGA segment obtained by factor Xa digestion (designated as r-PGA) possessed proteolytic activities equivalent to native PGA purified from gastric tissue (t-PGA). For PGCs (MBP-PGC, r-PGC and t-PGC) also, the specific activities were almost the same. However, the activities of PGCs were about 3-to 4-hold higher than those of PGAs. In PGA and PGC immunoassay systems, rPGs (r-PGA and r-PGC) and the EIA kit standard PGs (gastric mucosal PGs) exhibited a good correlation. From these results, r-PGs would seem to be applicable as assay standards without compromising the sensitivity of the immunoassay systems.

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Variable numbers of pepsinogen genes are located in the centromeric region of human chromosome 11 and determine the high-frequency electrophoretic polymorphism.

Cited by 66 publications

References 29 publications

Gastric chief cell‐specific transcription of the pepsinogen A gene

Gastric chief cell‐specific transcription of the pepsinogen A gene

Cloning of a human galactokinase gene (GK2) on chromosome 15 by complementation in yeast.

Purification of recombinant human pepsinogens and their application as immunoassay standards

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