MOLECULAR-BIOLOGY OF L-HISTIDINE DECARBOXYLASE

L-Histidine decarboxylase (HDC) catalyzes the formation of histamine f rom L-histidine. This biogenic amine is known to exert various effects in physiological and pathological reactions. In contrast to the well- known mechanism of histamine action through its interaction with speci fic receptors, the mechanisms regulating HDC gene expression are not e lucidated. We have purified HDC from mouse mastocytoma cells, and isol ated mouse HDC cDNA, and found that the primary translated product is posttranslationally processed to yield a mature active enzyme. In mast ocytoma cells, we demonstrated that the induction of HDC activity and HDC mRNA synergistically occurred on treatment with dexamethasone+TPA, and also cAMP+Ca2+. To clarify the mechanism of up-regulation by thes e stimuli of the transcription of the HDC gene, we have isolated a gen omic DNA clone encoding 5'-flanking region sequence and the first two exons. The transcription start site and the nucleotide sequences of th e promoter regions including TATA- and CC-boxes were determined. With mastocytoma cells transiently transfected with 5' deletion constructs of HDC-CAT fusion gene, it was found that the sequences from - 132 to - 53 and - 267 to - 53 are essential for the regulatory elements invol ved in the increased transcription of the HDC gene with dexamethasoneTPA and cAMP+Ca2+, respectively. Furthermore, we have isolated a genom ic DNA from human basophilic cells, and analysed its structure to eluc idate the mechanisms regulating the tissue specificity of HDC gene exp ression.