Five suppressor of presenilin (spr) genes have been identified in screens for suppressors of the egg-laying defect of mutations in the
sel-12 presenilin gene. Most spr genes encode nuclear factors that resemble components of the mammalian REST-CoREST transcriptional repressor complex that regulates neuronal gene expression. SPR-3 and SPR-4 are C <sub>2</sub>H <sub>2</sub> zinc finger proteins that weakly resemble the transcription factor REST, SPR-1 is the homolog of the scaffold and nucleosome binding protein CoREST, while SPR-5 is the homolog of LSD1, a lysine specific histone demethylase.
spr-2 encodes a Nucleosome Assembly Protein orthologous to the human SET/Taf-1beta. We have identified a new spr gene,
spr-6 , which encodes a protein of 366 amino acids that has no known domains and no clear orthologs outside of the nematodes. However, within the nematode phylum,
spr-6 genes appear to be conserved. Multiple sequence alignments of the predicted SPR-6 proteins in various species indicates that there are three conserved domains in the protein each of which has a divergent zinc finger domain with a C<sub>2</sub>HC signature. The biochemical function of SPR-6 is presently unclear, however an anti SPR-6 polyclonal antibody detects specific nuclear staining.
spr-6 mutations do not modify the phenotype of weak
lin-12 loss of function or gain of function alleles indicating that
spr-6 is unlikely to play a direct role in
lin-12 signaling. Rather, preliminary evidence suggest that, like
spr-1,
spr-3,
spr-4 and
spr-5, mutations in
spr-6 may suppress
sel-12 by de-repressing the transcription of a second presenilin gene,
hop-1. Consistent with this, the suppression of
sel-12 by
spr-6 is dependent on
hop-1 activity. On there own, all
spr-6 mutations reduce fertility, and some quite severely. The
pf38 allele also displays dead eggs and a Him phenotype which is an indicator of problems in chromosome segregation. Like mutations in
spr-5, mutations in
spr-6 can display a temperature sensitive mortal germline (Mrt) phenotype. That is, at 25C strains containing
spr-6 mutations tend to become sterile over multiple generations indicating a defect in the epigenetic maintenance of germline totipotency.