Fungal CSL transcription factors

We have identified putative CSL genes in several fungal species, showing that this family is not confined to metazoans. We have analyzed their sequence conservation and identified the presence of well-defined domains typical of genuine CSL proteins. Furthermore, we have shown that the candidate fungal protein sequences contain highly conserved regions known to be required for sequence-specific DNA binding in their metazoan counterparts. The phylogenetic analysis of the newly identified fungal CSL proteins revealed the existence of two distinct classes, both of which are present in all the species studied.Our findings support the evolutionary origin of the CSL transcription factor family in the last common ancestor of fungi and metazoans. We hypothesize that the ancestral CSL function involved DNA binding and Notch-independent regulation of transcription and that this function may still be shared, to a certain degree, by the present CSL family members from both fungi and metazoans.The CSL (CBF1/RBP-Jκ/Suppressor of Hairless/LAG-1) proteins compose a family of transcription factors essential for metazoan development [1,2]. They are present in all metazoan genomes studied and show remarkable sequence conservation across phylogeny. They localize predominantly or exclusively in the cell nucleus where they can either repress or activate transcription depending on the context and the presence of various coregulators. CSL proteins recognize a very tightly defined consensus sequence GTG(G/A)GAA in target promoters. Their best characterized function relates to the signaling pathway of the transmembrane receptor Notch where they mediate the effector nuclear step – activation of Notch-responsive genes. The Notch pathway regulates metazoan embryonic development, cell fate decisions and tissue boundaries specifications [2,3]. Its deregulation is implicated in several diseases including cancer [4] and, in addition, several viruses encode factors that misuse this pathway via intera