Binding of a pancreatic nuclear protein is correlated with amytase enhancer activity

Howard, Georgette; Keller, Paul R.; Meisler, Miriam H.

doi:10.1093/nar/17.20.8185

Cited by 26 publications

(37 citation statements)

References 26 publications

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“…This region of the mouse gene contains an enhancer element which is recognized by the pancreas-specific nuclear protein PTF1 (3,13). The rodent PTF1-binding sites are aligned with the human genes in Fig.…”

Section: Discussionmentioning

confidence: 99%

Retroviral and pseudogene insertion sites reveal the lineage of human salivary and pancreatic amylase genes from a single gene during primate evolution.

et al. 1990

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We have analyzed the junction regions of inserted elements within the human amylase gene complex. This complex contains five genes which are expressed at high levels either in the pancreas or in the parotid gland.The proximal 5'-flanking regions of these genes contain two inserted elements. A -y-actin pseudogene is located at a position 200 base pairs upstream of the first coding exon. All of the amylase genes contain this insert. The subsequent insertion of an endogenous retrovirus interrupted the -y-actin pseudogene within its 3'-untranslated region. Nucleotide sequence analysis of the inserted elements associated with each of the five human amylase genes has revealed a series of molecular events during the recent history of this gene family. The data indicate that the entire gene family was generated during primate evolution from one ancestral gene copy and that the retroviral insertion activated a cryptic promoter.The complete human amylase gene cluster has recently been cloned in our laboratory and by others (8,9,11,12,21). The cluster spans 230 kilobases (kb) on human chromosome 1. The most common human haplotype contains five intact genes: two pancreatic genes (AMY2A and AMY2B) and three salivary genes (AMYIA, AMYIB, and AMYIC) (8, 9). The salivary and pancreatic genes are 93% identical in the sequence of the proximal 718 base pairs (bp) of the 5'-flanking regions (12). Nonetheless, these genes are expressed with different tissue specifities. AMY2A and AMY2B transcripts are present in the human pancreas but not in the parotid salivary gland, while AMY] transcripts are present in the parotid gland but not in the pancreas (28).Two inserted elements have been identified in the 5' regions of the human amylase genes. A -y-actin pseudogene was identified 200 bp upstream of the first amylase-coding exon (4, 28). The promoter and nontranslated exon of the salivary amylase genes are derived from the y-actin pseudogene. Retroviral long terminal repeat (LTR) and gag sequences were also identified in the 5'-flanking region of an amylase gene (4). We subsequently determined the locations of a total of seven LTRs within the gene cluster (28). The mouse amylase gene cluster does not contain retroviral or -y-actin-related sequences (unpublished observations), indicating that insertion of both elements occurred subsequent to the separation of human and mouse.In the present report, we describe the junction regions of the y-actin and retroviral inserts upstream of each human amylase gene. These inserts provide unique molecular markers for the recent evolution of this gene family. The structural data suggest a specific sequence of events by which the five human amylase genes were generated from one ancestral gene within the past 40 million years. MATERIALS AND METHODSSequence analysis. Genomic DNA fragments from cosmids G6 (AMY2B), G45 Restriction fragments from cosmid G21 (9) were subcloned into pGEM 1 or 2 for preparation of riboprobe templates. The amylase probe was a 470-nucleotide HaeIII-EcoRI fragment containing exon...

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Section: Discussionmentioning

confidence: 99%

Retroviral and pseudogene insertion sites reveal the lineage of human salivary and pancreatic amylase genes from a single gene during primate evolution.

et al. 1990

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“…On the other hand, the region between À2300 and À1 bp of C57BL/6J mice was similar to that of C3H mice. Three binding sites were found in the 1 kb upstream region of the Prss1 gene 31,37 (Supplementary Figure 3). All these sequences are identical in all strains except one nucleotide change at À192 of the binding site (ATCACCTGCT) for nuclear protein in JF1 mice.…”

Section: Nucleotide Sequences Of 3 Kb Upstream Regions Of Spink3 and mentioning

confidence: 99%

Relationship of strain-dependent susceptibility to experimentally induced acute pancreatitis with regulation of Prss1 and Spink3 expression

Wang

Ohmuraya

Suyama

et al. 2010

Laboratory Investigation

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To analyze susceptibility to acute pancreatitis, five mouse strains including Japanese Fancy Mouse 1 (JF1), C57BL/6J, BALB/c, CBA/J, and C3H/HeJ were treated with either a cholecystokinin analog, cerulein, or a choline-deficient, ethioninesupplemented (CDE) diet. The severity of acute pancreatitis induced by cerulein was highest in C3H/HeJ and CBA/J, moderate in BALB/c, and mildest in C57BL/6J and JF1. Basal protein expression levels of the serine protease inhibitor, Kazal type 3 (Spink3) were higher in JF1 and C57BL/6J mice than those of the other three strains under normal feeding conditions. After treatment with cerulein, expression level of Spink3 increased remarkably in JF1 and mildly in C57BL/6J, BALB/c, CBA/J, and C3H/HeJ strains. Increased proteinase, serine, 1 (Prss1) protein expression accompanied by increased trypsin activity with cerulein treatment was observed in susceptible strains such as CBA/J and C3H/HeJ. Similar results were obtained with a CDE diet. In the 3 kb Spink3 promoter region, 92 or 8 nucleotide changes were found in JF1 or C3H vs C57BL/6J, respectively, whereas in the Prss1 promoter region 39 or 46 nucleotide changes were found in JF1 or C3H vs C57BL/6J, respectively. These results suggest that regulation of Prss1 and Spink3 expression is involved in the susceptibility to experimentally induced pancreatitis. The JF1 strain, which is derived from the Japanese wild mouse, will be useful to examine new mechanisms that may not be found in other laboratory mouse strains. Over 450 inbred strains of mice have been described, 1 providing a wealth of different genotypes and phenotypes for studying human diseases. Actually, the use of various breeding strategies in combination with positional cloning and positional candidate gene approach has led to the discovery of many genes that underlie human disease. 2 The Japanese wild mouse, belonging to Mus musculus molossinus, has several genetic characteristics clearly distinguishable from the European wild mouse, derived from M.m. domesticus. These subspecies were separated about one million years ago and about 1% of their genome sequences are different. [3][4][5][6][7][8] Therefore, strains MSM/Ms 9 and Japanese Fancy Mouse 1 (JF1), 10 which were established from M.m. molossinus, are powerful genetic resources to analyze disease processes.Many inbred strains have been bred for specific phenotypes. C57BL/6J mice are susceptible to high-fat diet-induced type II diabetes. 11 JF1 mice are especially sensitive to high-fat diet-induced diabetes and obesity, whereas MSM/Ms mice are resistant. 12 To date, however, there is little information about the difference in severity of pancreatitis among inbred strains of mice.Acute pancreatitis is an important disease that can be triggered by a variety of factors, including excessive alcohol consumption, 13-16 obstruction of the ampulla of Vater by gall stones, 17,18 and genetic factors. 19,20 Hereditary chronic pancreatitis is a rare form of early onset chronic pancreatitis, characterized by the onset of recurrent...

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“…1987). Comparison between the 5'-flanking regions of nine genes expressed in both the rat and mouse exocrine pancreas resulted in the identification of a family of short, related sequences located within the enhancer regions of these genes (Walker et al 1983;Swift et al 1984; Boulet et al 1986;Stevenson et al 1986;Howard et al 1989). Site-directed mutagenesis studies showed that these cis-acting sequences are actually involved in regulating the expression of tissue-specific genes through the binding of the specific pancreatic nuclear protein PTF1.…”

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confidence: 99%

Molecular aspects of enzyme synthesis in the exocrine pancreas with emphasis on development and nutritional regulation

Huërou‐Luron¹,

Lhoste

Wicker‐Planquart

et al. 1993

Proc. Nutr. Soc.

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Binding of a pancreatic nuclear protein is correlated with amytase enhancer activity

Cited by 26 publications

References 26 publications

Retroviral and pseudogene insertion sites reveal the lineage of human salivary and pancreatic amylase genes from a single gene during primate evolution.

Retroviral and pseudogene insertion sites reveal the lineage of human salivary and pancreatic amylase genes from a single gene during primate evolution.

Relationship of strain-dependent susceptibility to experimentally induced acute pancreatitis with regulation of Prss1 and Spink3 expression

Molecular aspects of enzyme synthesis in the exocrine pancreas with emphasis on development and nutritional regulation

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