The mouse L-histidine decarboxylase gene: structure and transcriptional regulation by CpG methylation in the promoter region (original) (raw)
Related papers
Journal of Biological Chemistry, 1998
L-Histidine decarboxylase (HDC) catalyzes the formation of histamine from L-histidine, and in hematopoietic cell lineages the gene is expressed only in mast cells and basophils. We attempted here to discover how HDC gene expression is restricted in these cells. In the cultured cell lines tested, only the mast cells and basophils strongly transcribed the HDC gene. However, in transient transfection analysis, the reporter constructs with the HDC promoter were active not only in expressing cells but also in nonexpressing cells. Detailed analyses of the HDC promoter region revealed that the GC box is essential for transactivation. Also, the promoter region of the HDC gene proved to be sensitive to DNase I and restriction endonucleases exclusively in HDC-expressing cells, suggesting that the promoter region is readily accessible to trans-acting factor(s). Furthermore, the promoter region in HDC-expressing cell lines was found to be selectively unmethylated. The correlation between HDC expression and hypomethylation was also found in primary human mast cells. Methylation of the HDC promoter in vitro reduced the luciferase reporter activity in transient expression analysis, suggesting that methylation of the promoter region is functionally important for HDC gene expression. These results imply that alteration of DNA methylation is one of the mechanisms regulating cell-specific expression of the HDC gene.
Mice lacking histidine decarboxylase exhibit abnormal mast cells
FEBS Letters, 2001
Histidine decarboxylase (HDC) synthesizes histamine from histidine in mammals. To evaluate the role of histamine, we generated HDC-deficient mice using a gene targeting method. The mice showed a histamine deficiency and lacked histaminesynthesizing activity from histidine. These HDC-deficient mice are viable and fertile but exhibit a decrease in the numbers of mast cells while the remaining mast cells show an altered morphology and reduced granular content. The amounts of mast cell granular proteases were tremendously reduced. The HDCdeficient mice provide a unique and promising model for studying the role of histamine in a broad range of normal and disease processes. ß
DNA methylation and gene expression
Microbiological reviews, 1991
A large body of evidence demonstrates that DNA methylation plays a role in gene regulation in animal cells. Not only is there a correlation between gene transcription and undermethylation, but also transfection experiments clearly show that the presence of methyl moieties inhibits gene expression in vivo. Furthermore, gene activation can be induced by treatment of cells with 5-azacytidine, a potent demethylating agent. Methylation appears to influence gene expression by affecting the interactions with DNA of both chromatin proteins and specific transcription factors. Although methylation patterns are very stable in somatic cells, the early embryo is characterized by large alterations in DNA modification. New methodologies are now becoming available for studying methylation at this stage and in the germ line. During development, tissue-specific genes undergo demethylation in their tissue of expression. In tissue culture cells this process is highly specific and appears to involve an ...
A structural gene (Hdc-s) for mouse kidney histidine decarboxylase
Biochemical Genetics, 1984
The concentration of mouse kidney histidine decarboxylase (HDC) is modulated by estrogen, testosterone, and thyroxine in a tissue-specific manner. Variation in HDC levels between strains of mice can be used to investigate the genetic regulation of(i) enzyme structure, (ii) tissue specific expression, and (iii) induction and repression by hormones. Variation in the structure of HDC between different inbred strains of mice affecting its Km for the cofactor pyridoxal-5'-phosphate (PLP) and its heat stability has been discovered. The alternative phenotypes are additively inherited in crosses and the heat stability difference is due to alleles of a single structural gene, Hdc-s, which segregate among the BXD and BXH recombinant inbred strains. The allele Hdc-s b determines the heat-stable phenotype (C57BL substrains), and the allele Hdc-s d the heat-labile phenotype (DBA/2 and C3H/He strains). The alleles of the structural gene cosegregate with alleles of a regulatory gene previously named Hdc (determining kidney enzyme concentration); there were no recombinants among 38 RI strains. Therefore the two loci are less than 0.685 cM apart and comprise part of the HDC gene complex, [Hdc], on chromosome 2 of the mouse.
Inhibition of promoter activity by methylation: possible involvement of protein mediators
Proceedings of the National Academy of Sciences of the United States of America, 1991
To study the relationship between DNA methylation and promoter activity we have methylated in vitro the promoters of the mouse metallothionein I gene and the herpes simplex virus thymidine kinase gene. We have transiently transfected these promoters fused to the human growth hormone in their methylated or unmethylated state into mouse L or F9 cells. Promoters methylated by methylase (M.) Hpa II and M.Hha I caused inhibition of reporter gene expression in L cells but not in F9 cells, while methylation of all CpGs by M.Sss I caused inhibition in both cell lines. Repression of promoter activity by M.Hpa II and M.Hha I methylation, but not by M.Sss I methylation, could be alleviated by cotransfection with an excess of untranscribable DNA methylated with M.Sss I. The methylated sites in nuclei isolated from the transfected L cells, but not F9 cells, were found to be protected from Msp I digestion. Taken together these results suggest that a factor present in L cells and missing in F9 cel...