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一组异染色质因子与小RNA通路协同作用，以对抗重复元件和生殖系应激。

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

作者信息

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

机构信息

The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.

出版信息

Elife. 2017 Mar 15;6:e21666. doi: 10.7554/eLife.21666.

DOI:10.7554/eLife.21666
PMID:28294943
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5395297/
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 of 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 /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.

摘要

转座子衍生的重复序列在真核生物基因组中占很大比例，必须使其沉默以保护基因组完整性。重复元件常存在于异染色质中；然而，人们对异染色质蛋白在重复序列调控中的作用和相互作用了解甚少。在这里，我们表明，多种异染色质蛋白与piRNA和核RNAi途径共同作用，使重复元件沉默，并防止生殖系中的基因毒性应激。编码HPL-2/HP1、LIN-13、LIN-61、LET-418/Mi-2和H3K9me2组蛋白甲基转移酶MET-2/SETDB1的基因突变体也表现出功能冗余的不育、生殖系凋亡增加、DNA修复缺陷以及与小RNA途径的相互作用。值得注意的是，通过抑制/p53、内源性减数分裂双链断裂或MIRAGE1 DNA转座子的表达，可以部分恢复异染色质突变体的生育能力。因子和途径之间的功能冗余是通过多种方式保护基因组的重要性的基础。

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