Comparative analysis of the human and mouse Hey1 promoter: Hey genes are new notch target genes

Hey genes (Hey1, Hey2 and HeyL) encode a new group of basic helix-loop-heli x transcription factors that are related to the hairy/Enhancer of split gen es. In the present study, we cloned and characterized the promoter region o f the human and mouse Hey1 gene, The transcription initiation site was loca ted 138 nucleotides upstream of the start codon. There is a minimal sequenc e element (nt -30 to -247) that is essential and important for basal transc ription in three different cell types. Further upstream, a highly conserved sequence block (nt -324 to -646; similar to 90% human/mouse similarity) co uld be identified that contains several putative binding sites for transcri ption factors and likely represents an important regulatory region for this gene, Cotransfection experiments demonstrated that the mHey1 promoter acti vity is up-regulated by the activated form of all four mammalian Notch rece ptors via two functional PCBP-J kappa binding sites, The other members of t he Hey gene family, Hey2 and HeyL, also possess RBP-J kappa binding sites a nd they are similarily responsive to Notch signaling. Thus, our data clearl y demonstrate that Hey genes form a new class of Notch signal transducers t hat should prove to be relevant in various developmental processes. (C) 200 0 Academic Press.