Regulation of Heterochromatin Assembly on Unpaired Chromosomes during Caenorhabditis elegans Meiosis by Components of a Small RNA-Mediated Pathway

• Type of Material: Article
• Authors: Xingyu She, Syracuse University; Alexander Fedotov, Emory University; William G Kelly, Emory University; Eleanor M. Maine, Syracuse University
• Language: English
• Date: 2009-08-28
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2009 She et al.
• Final Published Version (URL): http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000624
• Title of Journal or Parent Work: PLoS Genetics
• ISSN: 1553-7390
• Volume: 5
• Issue: 8
• Start Page: e1000624
• End Page: e1000624
• Grant/Funding Information: This work was supported by funds from the National Science Foundation (MCB-0615657) and Syracuse University to EMM, and by funds from the National Institutes of Health (RO1 GM063102) to WGK.; The Caenorhabditis Genetics Center, from which some nematode strains used in this study were obtained, is supported by funding from the NIH Center for Research Resources.
• Research Categories: Biology, Genetics; Biology, Cell

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.