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.
Ehrnsperger
Achim
A
Department of Hematology and Oncology, University of Regensburg, Franz-Josef Strauss Allee 11, 93042 Regensburg, Germany.
Rehli
Michael
M
Thu-Hang
Pham
P
Kreutz
Marina
M
D051722:ADAM Proteins; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D019483:Disintegrins / Q000235:genetics* / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000502:physiology*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*
D019483:Disintegrins; D005819:Genetic Markers; D014157:Transcription Factors; D051722:ADAM Proteins; C411902:ADAM19 protein, human; D008666:Metalloendopeptidases