A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress
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 of C. elegans heterochromatin 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 inhibiting cep-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.
Errataetall: | |
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Medienart: |
E-Artikel |
Erscheinungsjahr: |
2017 |
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Erschienen: |
2017 |
Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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Enthalten in: |
eLife - 6(2017) vom: 15. März |
Sprache: |
Englisch |
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Beteiligte Personen: |
McMurchy, Alicia N [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 24.04.2017 Date Revised 10.02.2024 published: Electronic ErratumIn: Elife. 2017 Oct 05;6:. - PMID 28980937 Citation Status MEDLINE |
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doi: |
10.7554/eLife.21666 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM269854754 |
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520 | |a 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 of C. elegans heterochromatin 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 inhibiting cep-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 | ||
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700 | 1 | |a Dong, Yan |e verfasserin |4 aut | |
700 | 1 | |a Aussianikava, Darya |e verfasserin |4 aut | |
700 | 1 | |a Appert, Alex |e verfasserin |4 aut | |
700 | 1 | |a Huang, Ni |e verfasserin |4 aut | |
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700 | 1 | |a Sapetschnig, Alexandra |e verfasserin |4 aut | |
700 | 1 | |a Miska, Eric A |e verfasserin |4 aut | |
700 | 1 | |a Ahringer, Julie |e verfasserin |4 aut | |
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