C. elegans HIM-17 links chromatin modification and competence for initiation of meiotic recombination.
Initiation of meiotic recombination by double-strand breaks (DSBs) must occur in a controlled fashion to avoid jeopardizing genome integrity. Here, we identify chromatin-associated protein HIM-17 as a link between chromatin state and DSB formation during C. elegans meiosis. Dependencies of several meiotic prophase events on HIM-17 parallel those seen for DSB-generating enzyme SPO-11: HIM-17 is essential for DSB formation but dispensable for homolog synapsis. Crossovers and chiasmata are eliminated in him-17 null mutants but are restored by artificially induced DSBs, indicating that all components required to convert DSBs into chiasmata are present. Unlike SPO-11, HIM-17 is also required for proper accumulation of histone H3 methylation at lysine 9 on meiotic prophase chromosomes. HIM-17 shares structural features with three proteins that interact genetically with LIN-35/Rb, a known component of chromatin-modifying complexes. Furthermore, DSB levels and incidence of chiasmata can be modulated by loss of LIN-35/Rb. These and other data suggest that chromatin state governs the timing of DSB competence.
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Kirthi C
KC
Reddy
Anne M
AM
Villeneuve
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism*; D002874:Chromosome Mapping; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism; D004706:Endodeoxyribonucleases; D004950:Esterases / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006657:Histones / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D007211:Indoles; D007621:Karyotyping; D008164:Luminescent Proteins / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D008540:Meiosis; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011418:Prophase; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D051135:Rad51 Recombinase; D011995:Recombination, Genetic; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D000099257:Meiotic Recombination Protein SPO11
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases; D004950:Esterases; D049452:Green Fluorescent Proteins; D006657:Histones; D007211:Indoles; D008164:Luminescent Proteins; D008239:Lysine; D051135:Rad51 Recombinase; D000099257:Meiotic Recombination Protein SPO11; C491265:HIM-17 protein, C elegans; C007293:DAPI; C495148:rad-51 protein, C elegans