We previously reported that the induction of L-histidine decarboxylase (HDC) in mouse mastocytoma cells was synergistically potentiated with a combination of dexamethasone and 12-O-tetradecanoylphorbol-13-acetate (TPA) [Biochim. Biophys. Acta, 1133, 172-178 (1992)]. To clarify the molecular mechanism of this synergistic action on HDC expression, we have isolated genomic DNA clone (MGH5), including 5′-flanking region of the mouse HDC gene. The transcription start site and the nucleotide sequences of the promoter regions were determined. We found that this clone contains a TATA-like box and a GC-box in the promoter region, and several putative binding sites for regulatory proteins in the 5′-flanking region. With mastocytoma cells transiently transfected with 5′ deletion constructs of HDC-CAT fusion gene, it was found that the sequence from -267 to -43 is essential for the regulatory element(s) involved in the increased transcription of the HDC gene with dexamethasone and TPA. © 1993 Academic Press, Inc.