title: 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.
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Duygu
authors.initials: D
authors.lastname: Yücel
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hoe
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Estelle
authors.initials: E
authors.lastname: Llamosas
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Sashi
authors.initials: S
authors.lastname: Kant
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Callum
authors.initials: C
authors.lastname: Jamieson
authors.affiliation: Australian Centre for Microscopy and Microanalysis, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Young
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Merlin
authors.initials: M
authors.lastname: Crossley
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia. Electronic address: hannah.nicholas@sydney.edu.au.
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Nicholas
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D051548:Histone Acetyltransferases / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D020798:Two-Hybrid System Techniques; D014844:Vulva / Q000196:embryology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; C000591591:SUMV-1 protein, C elegans; C075912:Lin-3 protein, C elegans; D004815:Epidermal Growth Factor; D051548:Histone Acetyltransferases
keywords: Caenorhabditis elegans; Chromatin; KAT8/MOF; Vulval development; synMuv