title: Regulation of heterochromatin assembly on unpaired chromosomes during Caenorhabditis elegans meiosis by components of a small RNA-mediated pathway.
abstract: Many organisms have a mechanism for down regulating the expression of non-synapsed chromosomes and chromosomal regions during meiosis. This phenomenon is thought to function in genome defense. During early meiosis in Caenorhabditis elegans, unpaired chromosomes (e.g., the male X chromosome) become enriched for a modification associated with heterochromatin and transcriptional repression, dimethylation of histone H3 on lysine 9 (H3K9me2). This enrichment requires activity of the cellular RNA-directed RNA polymerase, EGO-1. Here we use genetic mutation, RNA interference, immunofluorescence microscopy, fluorescence in situ hybridization, and molecular cloning methods to identify and analyze three additional regulators of meiotic H3K9me2 distribution: CSR-1 (a Piwi/PAZ/Argonaute protein), EKL-1 (a Tudor domain protein), and DRH-3 (a DEAH/D-box helicase). In csr-1, ekl-1, and drh-3 mutant males, we observed a reduction in H3K9me2 accumulation on the unpaired X chromosome and an increase in H3K9me2 accumulation on paired autosomes relative to controls. We observed a similar shift in H3K9me2 pattern in hermaphrodites that carry unpaired chromosomes. Based on several assays, we conclude that ectopic H3K9me2 accumulates on paired and synapsed chromosomes in these mutants. We propose alternative models for how a small RNA-mediated pathway may regulate H3K9me2 accumulation during meiosis. We also describe the germline phenotypes of csr-1, ekl-1, and drh-3 mutants. Our genetic data suggest that these factors, together with EGO-1, participate in a regulatory network to promote diverse aspects of development.
authors.affiliation: Department of Biology, Syracuse University, Syracuse, New York, United States of America.
authors.forename: Xingyu
authors.initials: X
authors.lastname: She
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.forename: Alexander
authors.initials: A
authors.lastname: Fedotov
authors.forename: William G
authors.initials: WG
authors.lastname: Kelly
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Maine
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002875:Chromosomes / Q000235:genetics*; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008297:Male; D008540:Meiosis; D008745:Methylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C529535:Ekl protein, c elegans; D006570:Heterochromatin; D006657:Histones; D034741:RNA, Small Interfering; C524398:Drh-3 protein, C elegans; C406772:EGO-1 protein, C elegans; D012324:RNA-Dependent RNA Polymerase; D053487:DEAD-box RNA Helicases