SUMV-1 antagonizes the activity of synthetic multivulva genes in Caenorhabditis elegans

Abstract

Chromatin regulators contribute to the developmental control of gene expression. In the nematode Caenorhabditis elegans, the roles of chromatin regulation in development have been explored in several contexts, including vulval differentiation. The synthetic multivulva (synMuv) genes are regulators of vulval development in C. elegans and the proteins encoded by these genes 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). We show that SUMV-1 is required in the hypodermis for the synMuv phenotype and that loss of sumv-1 function suppresses ectopic expression of lin-3 in synMuv mutant animals. In yeast two-hybrid assays SUMV-1 physically interacts with SUMV-2, and reduction of sumv-2 function also suppresses the synMuv phenotype. We identified similarities between SUMV-1 and SUMV-2 and mammalian proteins KAT8 NSL2 and KAT8 NSL3, respectively, which are components of the KAT8/MOF histone acetyltransferase complex. Reduction of function of mys-2, which encodes the enzymatic component of the KAT8/MOF complex, also suppresses the synMuv phenotype, and MYS-2 physically interacts with SUMV-2 in yeast two-hybrid assays. Together these observations suggest that SUMV-1 and SUMV-2 may function together with MYS-2 in a nematode KAT8/MOF-like complex to antagonise the activity of the synMuv genes.

A Network of Chromatin Factors Is Regulating the Transition to Postembryonic Development inCaenorhabditis elegans

“…We also identified the two genes, sumv-1 and sumv-2 , whose protein products are members of a putative worm KAT8/MOF histone acetyltransferase complex ( Rea et al 2007 ). This chromatin-activating complex is known to play a role during vulval development ( Yucel et al 2014 ).…”

Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3S HDAC complex in C. elegans

“…Previous genetic studies further support both unique and common functions for components of these complexes and other proteins isolated in our proteomics approach. For example, inactivation of the SIN3 complex subunits sin-3 and mrg-1 , the NSL complex subunits sumv-1 and sumv-2 , and the SET-2/SET1 complex subunits cfp-1, wdr-5.1 and dpy-30 , but not set-2 , can all suppress the synthetic multivulval (SynMuv) phenotype resulting from mutations in repressive chromatin factors (119,120). A subset of these genes, including sin-3 , mrg-1, wdr-5.1 and dpy-30 , but neither set-2 nor cfp-1 , also suppress the larval lethality resulting from inactivation of lin-35 /Rb in a sensitized background (121).…”

Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3 HDAC complex

“…Previous studies further support common functions for these complexes and other proteins isolated in our proteomics approach. For example, inactivation of the SET-2/SET1 complex subunits cfp-1, wdr-5.1, dpy-30, the SIN3 complex subunits sin-3 and mrg-1, and the NSL complex subunits sumv-1 and sumv-2 can all suppress the synthetic multivulval (SynMuv) phenotype resulting from mutations in repressive chromatin factors including homologs of the Mi2/NuRD complex, and the Heterochromatin Protein 1 (HP1) homologue HPL-2 (Cui et al 2006;Yücel et al 2014). A subset of these genes, including dpy-30, wdr-5 mrg-1 and sin-3 also suppress the larval lethality resulting from inactivation of lin-35/Rb in a sensitized background (Fay and Yochem 2007).…”