Enhancer of split, a Drosophila orthologue of HES, is a basic-helix-loop-helix (bHLH) protein that represses transcription during Drosophila nervous system development. Groucho, the Drosophila homologue of TLE proteins, binds to the WRPW motif of Enhancer of split, resulting in the formation of a transcriptional co-repressor involved in the regulation of neurogenesis, segmentation and sex determination (Paroush et al. 1994). The interaction of HES1 and TLE proteins is conserved in mammals and the WRPW motif of HES1 plays the key role in the formation of HES1:TLE complex (Fisher et al. 1996, Grbavec and Stifani 1996).