title: A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress.
abstract: Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set ofC. elegansheterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways. Remarkably, fertility of heterochromatin mutants could be partially restored by inhibitingcep-1/p53, endogenous meiotic double strand breaks, or the expression of MIRAGE1 DNA transposons. Functional redundancy among factors and pathways underlies the importance of safeguarding the genome through multiple means.
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Alicia N
authors.identifier: 0000-0002-7033-8790
authors.initials: AN
authors.lastname: McMurchy
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Przemyslaw
authors.identifier: 0000-0002-9464-7475
authors.initials: P
authors.lastname: Stempor
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Tessa
authors.initials: T
authors.lastname: Gaarenstroom
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Brian
authors.initials: B
authors.lastname: Wysolmerski
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Darya
authors.initials: D
authors.lastname: Aussianikava
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Alex
authors.initials: A
authors.lastname: Appert
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Ni
authors.identifier: 0000-0001-8849-038X
authors.initials: N
authors.lastname: Huang
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Paulina
authors.initials: P
authors.lastname: Kolasinska-Zwierz
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sapetschnig
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Eric A
authors.identifier: 0000-0002-4450-576X
authors.initials: EA
authors.lastname: Miska
authors.affiliation: The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Julie
authors.identifier: 0000-0002-7074-4051
authors.initials: J
authors.lastname: Ahringer
mesh_terms: D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004260:DNA Repair; D005786:Gene Expression Regulation; D005854:Germ Cells / Q000502:physiology; D006570:Heterochromatin / Q000378:metabolism*; D020071:Interspersed Repetitive Sequences; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D034741:RNA, Small Interfering
keywords: C. elegans; DNA damage; chromosomes; evolutionary biology; genes; genomics; germ line; heterochromatin; nuclear RNAi; piRNA; repetitive elements