Histone H3K9 methylation is dispensable for Caenorhabditis elegans development but suppresses RNA:DNA hybrid-associated repeat instability.
Histone H3 lysine 9 (H3K9) methylation is a conserved modification that generally represses transcription. In Caenorhabditis elegans it is enriched on silent tissue-specific genes and repetitive elements. In met-2 set-25 double mutants, which lack all H3K9 methylation (H3K9me), embryos differentiate normally, although mutant adults are sterile owing to extensive DNA-damage-driven apoptosis in the germ line. Transposons and simple repeats are derepressed in both germline and somatic tissues. This unprogrammed transcription correlates with increased rates of repeat-specific insertions and deletions, copy number variation, R loops and enhanced sensitivity to replication stress. We propose that H3K9me2 or H3K9me3 stabilizes and protects repeat-rich genomes by suppressing transcription-induced replication stress.
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.|Faculty of Natural Sciences, University of Basel, Basel, Switzerland.
Peter
P
Zeller
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Jan
J
Padeken
Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Robin
R
van Schendel
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Veronique
V
Kalck
Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Marcel
M
Tijsterman
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.|Faculty of Natural Sciences, University of Basel, Basel, Switzerland.
Susan M
SM
Gasser
D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D018509:DNA, Helminth / Q000378:metabolism; D005298:Fertility; D017238:Genes, Helminth; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D020071:Interspersed Repetitive Sequences; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D009693:Nucleic Acid Hybridization; D020871:RNA Stability; D018510:RNA, Helminth / Q000378:metabolism; D013696:Temperature
D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; D006657:Histones; D018510:RNA, Helminth; D011495:Histone-Lysine N-Methyltransferase; C523531:Met-2 protein, C elegans; C000622377:SET-25 protein, C elegans; D008239:Lysine