title: dSet1 is the main H3K4 di- and tri-methyltransferase throughout Drosophila development.
abstract: In eukaryotes, the post-translational addition of methyl groups to histone H3 lysine 4 (H3K4) plays key roles in maintenance and establishment of appropriate gene expression patterns and chromatin states. We report here that an essential locus within chromosome 3L centric heterochromatin encodes the previously uncharacterized Drosophila melanogaster ortholog (dSet1, CG40351) of the Set1 H3K4 histone methyltransferase (HMT). Our results suggest that dSet1 acts as a "global" or general H3K4 di- and trimethyl HMT in Drosophila. Levels of H3K4 di- and trimethylation are significantly reduced in dSet1 mutants during late larval and post-larval stages, but not in animals carrying mutations in genes encoding other well-characterized H3K4 HMTs such as trr, trx, and ash1. The latter results suggest that Trr, Trx, and Ash1 may play more specific roles in regulating key cellular targets and pathways and/or act as global H3K4 HMTs earlier in development. In yeast and mammalian cells, the HMT activity of Set1 proteins is mediated through an evolutionarily conserved protein complex known as Complex of Proteins Associated with Set1 (COMPASS). We present biochemical evidence that dSet1 interacts with members of a putative Drosophila COMPASS complex and genetic evidence that these members are functionally required for H3K4 methylation. Taken together, our results suggest that dSet1 is responsible for the bulk of H3K4 di- and trimethylation throughout Drosophila development, thus providing a model system for better understanding the requirements for and functions of these modifications in metazoans.
authors: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
authors: Graham
authors: G
authors: Hallson
authors: Robert E
authors: RE
authors: Hollebakken
authors: Taosui
authors: T
authors: Li
authors: Monika
authors: M
authors: Syrzycka
authors: Inho
authors: I
authors: Kim
authors: Shawn
authors: S
authors: Cotsworth
authors: Kathleen A
authors: KA
authors: Fitzpatrick
authors: Donald A R
authors: DA
authors: Sinclair
authors: Barry M
authors: BM
authors: Honda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002874:Chromosome Mapping; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000201:enzymology* / Q000235:genetics; D005786:Gene Expression Regulation; D023061:Gene Order; D005804:Genes, Lethal; D056426:Genetic Loci; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D019076:Transgenes
chemical_list: C490910:ASH1 protein, Drosophila; D051017:Apoptosis Regulatory Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones; C570297:Set protein, Drosophila; D014157:Transcription Factors; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C479519:TRR protein, Drosophila