title: Spp1, a member of the Set1 Complex, promotes meiotic DSB formation in promoters by tethering histone H3K4 methylation sites to chromosome axes.
abstract: Meiotic chromosomes are organized into arrays of loops that are anchored to the chromosome axis structure. Programmed DNA double-strand breaks (DSBs) that initiate meiotic recombination, catalyzed by Spo11 and accessory DSB proteins, form in loop sequences in promoters, whereas the DSB proteins are located on chromosome axes. Mechanisms bridging these two chromosomal regions for DSB formation have remained elusive. Here we show that Spp1, a conserved member of the histone H3K4 methyltransferase Set1 complex, is required for normal levels of DSB formation and is associated with chromosome axes during meiosis, where it physically interacts with the Mer2 DSB protein. The PHD finger module of Spp1, which reads H3K4 methylation close to promoters, promotes DSB formation by tethering these regions to chromosome axes and activating cleavage by the DSB proteins. This paper provides the molecular mechanism linking DSB sequences to chromosome axes and explains why H3K4 methylation is important for meiotic recombination.
authors.affiliation: Institut Curie, Centre de Recherche, 75248 Paris, France.
authors.forename: Vérane
authors.initials: V
authors.lastname: Sommermeyer
authors.forename: Claire
authors.initials: C
authors.lastname: Béneut
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Chaplais
authors.forename: Maria Elisabetta
authors.initials: ME
authors.lastname: Serrentino
authors.forename: Valérie
authors.initials: V
authors.lastname: Borde
mesh_terms: D015825:Chromosomes, Fungal / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008540:Meiosis; D008745:Methylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D000099257:Meiotic Recombination Protein SPO11
chemical_list: D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones; D012319:RNA Polymerase II; D029701:Saccharomyces cerevisiae Proteins; C071054:REC107 protein, S cerevisiae; C524367:SPP1 protein, S cerevisiae; C411250:SET1 protein, S cerevisiae; C518938:Spo11 protein, S cerevisiae; D000099257:Meiotic Recombination Protein SPO11