Characterization of the human and mouse HEY1, HEY2, and HEYL genes: Cloning, mapping, and mutation screening of a new bHLH gene family

Many basic helix-loop-helix (bHLH) transcription factors are known as key r egulators of embryonic development or differentiation in various species. W e have isolated and characterized three new hairy-related bHLH transcriptio n factor genes from mouse and human (hairy and Enhancer-of-split related wi th YRPW motif; HEY1, HEY2, and HEYL). All three HEP genes have a similar ge nomic structure with five exons. Together with a highly related Drosophila homologue, they form a new bHLH gene subfamily that is different from both hairy and the known vertebrate Hes and Her genes. While the overall structu re with the bHLH domain, Orange domain, and WRPW motif is similar, the last motif is changed to KPYRPWG in Hey1/2 and absent in HeyL. This and other s equence features suggest Hey proteins to have unique functional properties. The genes were mapped by fluorescence in situ hybridization and RH mapping to the following human chromosomes: (HEY1) 8q21, (HEY2) 6q21, and (HEYL) 1 p34.3. Based on expression patterns and map location, HEY genes are candida tes for several human or mouse disease loci. However, initial screening of DNA from affected individuals for two human disorders and four mouse mutant s did not reveal any diagnostic alterations in the coding regions. (C) 2000 Academic Press.