Analysis of promoter regions in Hailey-Hailey disease and Darier's disease genes.

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Results obtained by research in 2003.1) We have identified 6 SNPs on the promoter region (from non-cording to -1200bp) of ATP2C1 (Hailey-Hailey disease (HHD) gene). There was no correlation between these SNPs and disease phenotypes of HHD.2) Various segments of promoter region of ATP2C1 were cloned into Luciferase vector, and reporter assay was performed using HaCat cell. We have identified +22 to +60 by segment as a expression controlling element for ATP2C1. Additional gel-sift assay utilizing antibodies and mutant decoy DNA segments revealed that two transcription factors, SP-1 and YY-1, could bind to this promoter region.Results obtained by research in 2004.1) Co-transfection of ATP2C1 promoter and SP-1 or YY-1 clone into the cells stimulated the expression of ATP2C1.2) Expression of SP-1 itself was up regulated by raised extracellular calcium concentration in the culture of HaCat cells.3) Expression of SP-1 was low in HHD keratinocytes and did not respond to raised extracellular calcium concentration in the culture due to abnormally stable-high level of calcium concentration in the cytosole of the cells caused by genetic mutation of ATP2C1.