The synMuv genes encode conserved chromatin interacting proteins which antagonize vulval cell fate specification. Until recently, the prevailing view to explain the action of this group of genes was that they are part of an inhibitory signal from
hyp7 which opposes the action of the inductive Ras signaling pathway. Recent data has challenged this view by showing that some SynMuvB genes, including
lin-35 Rb, are likely to function within the
hyp7 syncytium to repress ectopic expression of the VPC inducer, LIN-3 (Cui et al., 2006a). In this model, the absence of SynMuv function leads to the improper secretion of LIN-3 from the hypodermis, leading to the induction of P3.p, P4.p, and P.8p, the VPCs that are normally not induced by LIN-3 from the anchor cell. Genetic mosaic analyses also support a
hyp7 focus for the Class B gene
lin-37, but a VPC focus for the Class B gene
lin-36 . These results suggest that that different SynMuvA and B genes may have different cellular foci. Genetic studies have shown that, depending on the temperature,
hpl-2 may act in both synMuvA and B pathways, suggesting this protein might be required more broadly for the transcriptional repression of genes necessary for proper vulval development. Biochemical analysis identified two synMuvB complexes in embryonic extracts : one containing LIN-35Rb and the chromatin-associated proteins LIN-9 and RbAp48/LIN-53, as well as a number of other conserved proteins, and a second complex with a composition similar to that of the mammalian Nucleosome Remodeling and Deacetylase complex. HPL-2 was not detected in either one of these complexes. To gain insight into how
hpl-2 interacts with other synMuv genes, we carried out experiments to establish the cellular focus of HPL-2/HP1. Surprisingly, we find that HPL-2 activity is required in both VPCs and HYP7 for correct vulval cell fate specification. In HYP7, HPL-2 acts through
lin-3, as shown for other synMuv genes. However, in VPCs, HPL-2 may act through an alternative, non LIN-3-associated mechanism. Furthemore, these results suggest that although in the absence of HPL-2 activity, ectopic expression of
lin-3 above a threshold level in the hypodermis is sufficient to induce ectopic vulva induction, HPL-2 can also act cell autonomously in VPCs to antagonize
lin-3/EGF signalling, presumably at the level of transcription of yet to be identified target genes. This latter function is likely to be independent of
lin-35 and other synMuv genes whose focus for vulval cell fate specification is in the hypodermis. These results suggest that there must be additional factors that contribute to the Muv phenotype in an
hpl-2;synMuvA context.