Epigenetic regulation of the dendritic cell-marker gene ADAM19.

Human ADAM19 (MADDAM) is a molecular marker for human dendritic cells and not expressed in macrophages. To investigate its cell-type-specific expression, we defined the transcriptional start site and the proximal promoter. Sequence analysis of the promoter revealed putative binding sites for several transcription factors including Sp1, Sp3, NF-kappaB, and VDR. A minimal promoter construct of 150 bp showed little difference in reporter activity between macrophages and dendritic cells. Transfection of monocytic THP-1 with the 150-bp fragment also resulted in significant reporter activity, despite the lack of endogenous MADDAM expression. TSA, a known inhibitor of histone deacetylation, led to a dose-dependent induction of MADDAM mRNA in THP-1. ChIP assays demonstrated high levels of acetylated histone H3 in the proximal promoter region of the MADDAM gene in TSA-treated THP-1 cells and dendritic cells as compared to macrophages, indicating an important role of histone acetylation in the regulation of the MADDAM gene.