THE GCM-MOTIF - A NOVEL DNA-BINDING MOTIF CONSERVED IN DROSOPHILA ANDMAMMALS

In the Drosophila nervous system, the glial cells missing gene (gcm) i s transiently expressed in glial precursors to switch their fate from the neuronal default to glia. It encodes a novel 504-amino acid protei n with a nuclear localization signal. We report here that the GCM prot ein is a novel DNA-binding protein and that its DNA-binding activity i s localized in the N-terminal 181 amino acids. It binds with high spec ificity to the nucleotide sequence, (A/G)CCCGCAT, which is a novel seq uence among known targets of DNA-binding proteins. Eleven such GCM-bin ding sequences are found in the 5' upstream region of the repo gene, w hose expression in early glial cells is dependent on gcm. This suggest s that the GCM protein is a transcriptional regulator directly control ling repo. We have also identified homologous genes from human and mou se whose products share a highly conserved N-terminal region with Dros ophila GCM. At least one of these was shown to have DNA-binding activi ty similar to that of GCM. By comparing the deduced amino acid sequenc es of these gene products, we were able to define the ''gem motif,'' a n evolutionarily conserved motif with DNA-binding activity. By PCR amp lification, we obtained evidence for the existence of additional gcm-m otif genes in mouse as well as in Drosophila. The gcm-motif, therefore , forms a family of novel DNA-binding proteins, and may function in va rious aspects of cell fate determination.