Mast cell-/basophil-specific transcriptional regulation of human L- histidine decarboxylase gene by CpG methylation in the promoter region

Atsuo Kuramasu, Hirohisa Saito, Satsuki Suzuki, Takehiko Watanabe, Hiroshi Ohtsu

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)31607-31614
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number47
DOIs
Publication statusPublished - 1998 Nov 20

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Mast cell-/basophil-specific transcriptional regulation of human L- histidine decarboxylase gene by CpG methylation in the promoter region'. Together they form a unique fingerprint.

Cite this