title: Caenorhabditis elegans chromatin-associated proteins SET-2 and ASH-2 are differentially required for histone H3 Lys 4 methylation in embryos and adult germ cells.
abstract: Methylation of histone H3 lysine 4 (H3K4me), a mark associated with gene activation, is mediated by SET1 and the related mixed lineage leukemia (MLL) histone methyltransferases (HMTs) across species. Mammals contain seven H3K4 HMTs, Set1A, Set1B, and MLL1-MLL5. The activity of SET1 and MLL proteins relies on protein-protein interactions within large multisubunit complexes that include three core components: RbBP5, Ash2L, and WDR5. It remains unclear how the composition and specificity of these complexes varies between cell types and during development. Caenorhabditis elegans contains one SET1 protein, SET-2, one MLL-like protein, SET-16, and single homologs of RbBP5, Ash2L, and WDR5. Here we show that SET-2 is responsible for the majority of bulk H3K4 methylation at all developmental stages. However, SET-2 and absent, small, or homeotic discs 2 (ASH-2) are differentially required for tri- and dimethylation of H3K4 (H3K4me3 and -me2) in embryos and adult germ cells. In embryos, whereas efficient H3K4me3 requires both SET-2 and ASH-2, H3K4me2 relies mostly on ASH-2. In adult germ cells by contrast, SET-2 serves a major role whereas ASH-2 is dispensable for H3K4me3 and most H3K4me2. Loss of SET-2 results in progressive sterility over several generations, suggesting an important function in the maintenance of a functional germ line. This study demonstrates that individual subunits of SET1-related complexes can show tissue specificity and developmental regulation and establishes C. elegans as a model to study SET1-related complexes in a multicellular organism.
authors.affiliation: Laboratory of Molecular and Cellular Biology, UMR5239 CNRS, Ecole Normale Supérieure de Lyon, 69007 Lyon, France.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiao
authors.forename: Cécile
authors.initials: C
authors.lastname: Bedet
authors.forename: Valérie J P
authors.initials: VJ
authors.lastname: Robert
authors.forename: Thomas
authors.initials: T
authors.lastname: Simonet
authors.forename: Steve
authors.initials: S
authors.lastname: Dunkelbarger
authors.forename: Cédric
authors.initials: C
authors.lastname: Rakotomalala
authors.forename: Gwen
authors.initials: G
authors.lastname: Soete
authors.forename: Hendrik C
authors.initials: HC
authors.lastname: Korswagen
authors.forename: Susan
authors.initials: S
authors.lastname: Strome
authors.forename: Francesca
authors.initials: F
authors.lastname: Palladino
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D005854:Germ Cells / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D009687:Nuclear Proteins / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D006657:Histones; D009687:Nuclear Proteins; C449640:SET-2 protein, C elegans; D029701:Saccharomyces cerevisiae Proteins; C551693:ASH-2 protein, C elegans; D011495:Histone-Lysine N-Methyltransferase; C411250:SET1 protein, S cerevisiae; D008239:Lysine