%0 Journal Article
%T Characterization of the human DYRK1A promoter and its regulation by the transcription factor E2F1
%A Barbara Maenz
%A Paul Hekerman
%A Eva M Vela
%A Juan Galceran
%A Walter Becker
%J BMC Molecular Biology
%D 2008
%I BioMed Central
%R 10.1186/1471-2199-9-30
%X Transcription start sites of the human DYRK1A gene are distributed over 800 bp within a region previously identified as an unmethylated CpG island. We have identified a new alternative noncoding 5'-exon of the DYRK1A gene which is located 772 bp upstream of the previously described transcription start site. Transcription of the two splicing variants is controlled by non-overlapping promoter regions that can independently drive reporter gene expression. We found no evidence of cell- or tissue-specific promoter usage, but the two promoter regions differed in their activity and their regulation. The sequence upstream of exon 1A (promoter region A) induced about 10-fold higher reporter gene activity than the sequence upstream of exon 1B (promoter region B). Overexpression of the transcription factor E2F1 increased DYRK1A mRNA levels in Saos2 and Phoenix cells and enhanced the activity of promoter region B three- to fourfold.The identification of two alternatively spliced transcripts whose transcription is initiated from differentially regulated promoters regions indicates that the expression of the DYRK1A gene is subject to complex control mechanisms. The regulatory effect of E2F1 suggests that DYRK1A may play a role in cell cycle regulation or apoptosis.Protein kinases of the DYRK (dual specificity tyrosine phosphorylation-regulated kinase) family play key roles in the regulation of cell growth and differentiation in a variety of systems [1,2]. Processes controlled by DYRKs include the organization of the symmetric cell division in S. pombe [3], the transition from growth to development in Dictyostelium [4], the formation of the embryonic axis in C. elegans [5], and the control of erythropoiesis in mammals [6]. In Drosophila, the kinase encoded by the minibrain gene (MNB) plays an essential role in postembryonic neurogenesis [7], and the orthologous proteins in chicken (MNB) and mammals (DYRK1A) have also been implicated in the regulation of neuronal differentiation (r
%U http://www.biomedcentral.com/1471-2199/9/30