A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress

作者:McMurchy Alicia N; Stempor Przemyslaw; Gaarenstroom Tessa; Wysolmerski Brian; Dong Yan; Aussianikava Darya; Appert Alex; Huang Ni; Kolasinska Zwierz Paulina; Sapetschnig Alexandra; Miska Eric A; Ahringer Julie
来源:eLife, 2017, 6: e21666.
DOI:10.7554/eLife.21666

摘要

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, LIN61, 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.

  • 出版日期2017-3-15