Chromatin regulators contribute to the developmental control of gene expression. The synthetic Multivulva (synMuv) genes are regulators of vulval development in the nematode Caenorhabditis elegans and the proteins that they encode include components of several histone modification and chromatin remodelling complexes. By inhibiting ectopic expression of the epidermal growth factor (LIN-3) in the nematode hypodermis, the synMuv genes prevent inappropriate vulval induction. In a forward genetic screen for modifiers of the expression of a hypodermal reporter gene, we identified a mutation that results in increased expression of the reporter. This mutation also suppresses ectopic vulval induction in synMuv mutants and we have consequently named the affected gene suppressor of synthetic Multivulva-1 (sumv-1). Using a fluorescent reporter to monitor vulval precursor cell induction, we found that sumv-1 additionally plays a role in normal vulval development.
We have identified similarity between the SUMV-1 protein and a mammalian protein called KAT8 NSL2, which is a functionally-uncharacterised component of the KAT8/MOF H4K16 acetyltransferase complex. Another uncharacterised component of this complex is KAT8 NSL3, for which the nematode homologue is SUMV-2. Through yeast two-hybrid assays we have found that SUMV-1 and SUMV-2 physically interact. Furthermore, reduction of function of SUMV-2 also suppresses the synMuv phenotype, as does reduction of function of MYS-2, the nematode homologue of KAT8/MOF. Together these data suggest that SUMV-1 and SUMV-2 function together with MYS-2 in a nematode KAT8/MOF-like histone acetyltransferase complex to antagonise the activity of the synMuv genes through the regulation of chromatin.