Mutations in the spr genes (for suppressor of presenilin) genetically bypass the need for the
sel-12 presenilin gene by de-repressing the transcription of a second functionally redundant presenilin gene,
hop-1. Five spr genes have previously been cloned and they encode proteins predicted to play a role in chromatin modification.
spr-1 and
spr-5 encode homologues of core components of the CoREST corepressor complex.
spr-1 encodes a homologue of the ELM2 and SANT domain containing protein CoREST, while
spr-5 is a polyamine oxidase-like protein. SPR-5 is homologous to LSD1, which was recently shown to have histone demethylase activity.
spr-3 and
spr-4 encode nematode specific C2H2 zinc finger proteins with weak similarity to the mammalian repressor protein REST. This suggests that the SPR Proteins may form a complex similar to the REST-CoREST complex.
spr-2 encodes a nucleosome assembly protein homologous to the mammalian SET/Taf-1beta gene suggesting that SPR-2 may interact with the other SPR proteins.As the screens that identified
spr-1 to
spr-5 appear to be very specific for components of a novel chromatin modifying complex (or complexes), we are trying to saturate the screen to identify additional components of the putative SPR complex. In screens for
dog-1 induced mutations (see abstract by Lakowski et al.), we have identified seven small deletions in the
spr-3 gene and one allele of
spr-4. In a large-scale high temperature EMS screen we have identified 39 new spr mutations. At least seven of these mutations appear to be temperature sensitive, which should aid in the further characterisation of the spr genes. We have assigned 22 of the new EMS induced mutations to genes and sequenced 14 of these. We have recovered new mutations in all of the previously identified spr genes as well as in at least three new genes. We have also recovered several mutations in
sel-10 which had previously been shown to suppress
sel-12. We have recently cloned
spr-6 and are rapidly closing in on the molecular identities of
spr-7 and 8.