The synthetic Multivulva (synMuv) genes are grouped into at least three functionally redundant classes, A, B, and C, that negatively regulate the specification of vulval cell fates. Animals mutant for one or more genes within the same class are non-Muv. Animals mutant for genes within any two classes are Muv. Some of the identified class B gene products are homologs of members of at least two transcriptional repression complexes.To identify loci that interact genetically with the synMuv genes, we performed two screens for synMuv suppressors. From these screens, we isolated 166 suppressors of the synMuv phenotype of lin-15AB
(n765ts) animals and 43 suppressors of the synMuv phenotype of
lin-53(
n833);
lin-15A(
n767) animals. The synMuv suppressor
isw-1 may act with the genes encoding homologs of the Drosophila NURF complex to antagonize the synMuv phenotype, because loss of the NURF301 and NURF38 homologs suppresses the synMuv phenotype of lin-15AB
(n765ts) animals. In our characterization of histone methyltransferase genes (see abstract by Andersen and Horvitz), we found that
mes-2 and
mes-4 are synMuv suppressors. Loss-of-function mutations in
mes-3 and
mes-6 but not
mes-1 suppress the synMuv phenotype. MES-2 and MES-6 are homologs of the Polycomb proteins E(z) and ESC, respectively. The Strome laboratory has shown that MES-2, MES-3, and MES-6 form a complex in embryos, methylate histone H3 lysine 27, and may play a role in the localization of MES-4. We are currently investigating how histone methylation can influence the synMuv phenotype and whether the predicted NURF complex homologs and the mes genes interact. We identified
lst-3(
n2070) as a dominant suppressor of the synMuv phenotype of lin-15AB
(n765ts) mutants. The Greenwald laboratory has implicated
lst-3 through bioinformatics as a putative target gene of LAG-1, a
lin-12 and
glp-1 Notch effector, and postulated that it may mediate the interplay between the RTK/Ras and Notch signal transduction pathways. The dominant phenotype conferred by
lst-3(
n2070) affects the putative DNA-binding domain and may increase wild-type function. We isolated several nonsense cis-dominant suppressor alleles and a deletion allele to study loss of
lst-3 function. Putative null mutations of
lst-3 confer a synMuv phenotype in combination with mutations in class A but not class B synMuv genes. These gain-of-function and loss-of-function alleles of
lst-3 may allow for a genetic analysis of the interplay between the RTK/Ras, Notch, and synMuv pathways.