piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans.

piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans.
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DOI:
10.1016/j.cell.2012.06.018
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发表时间:
2012-07-06
期刊:
影响因子:
64.5
通讯作者:
Miska EA
Miska EA
中科院分区:
生物学1区
文献类型:
--
作者:
Ashe A;Sapetschnig A;Weick EM;Mitchell J;Bagijn MP;Cording AC;Doebley AL;Goldstein LD;Lehrbach NJ;Le Pen J;Pintacuda G;Sakaguchi A;Sarkies P;Ahmed S;Miska EA

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转基因作用对人类健康,生物学适应性和进化具有广泛的影响,但是,它们的机制和生物学的理解仍然很少,我们证明了生殖线核小RNA/染色质途径可以在多代人中触发的核RNA触发的核心反应,从而可以使用核RNA依赖于核心。 RNAi和染色质因素是环境RNAi和Pirna沉默的多代因子。独立于PIRNA触发器,但仍取决于核RNAi/染色质途径。 ►在相同的核沉默途径上汇聚多代遗传和PIRNA►hrde1/wago-9和pirna静音所需的染色质因子►piRNAS可以诱导多代沉默,但仍与20代相关的核心持续记忆相关。 多代遗传和PIRNA在同一沉默途径上汇聚,其中核wagos和染色质因子都可能会丢失。
Transgenerational effects have wide-ranging implications for human health, biological adaptation, and evolution; however, their mechanisms and biology remain poorly understood. Here, we demonstrate that a germline nuclear small RNA/chromatin pathway can maintain stable inheritance for many generations when triggered by a piRNA-dependent foreign RNA response in C. elegans. Using forward genetic screens and candidate approaches, we find that a core set of nuclear RNAi and chromatin factors is required for multigenerational inheritance of environmental RNAi and piRNA silencing. These include a germline-specific nuclear Argonaute HRDE1/WAGO-9, a HP1 ortholog HPL-2, and two putative histone methyltransferases, SET-25 and SET-32. piRNAs can trigger highly stable long-term silencing lasting at least 20 generations. Once established, this long-term memory becomes independent of the piRNA trigger but remains dependent on the nuclear RNAi/chromatin pathway. Our data present a multigenerational epigenetic inheritance mechanism induced by piRNAs. ► Multigenerational inheritance and piRNAs converge on same nuclear silencing pathway ► HRDE1/WAGO-9 and chromatin factors required for inheritance of piRNA silencing ► piRNAs can induce multigenerational silencing for more than 20 generations. ► Long-term memory independent of piRNA triggers but remains dependent on nuclear pathway Multigenerational inheritance and piRNAs converge on same silencing pathway, in which both nuclear WAGOs and chromatin factors are required. The piRNA trigger can be lost, but the nuclear silencing pathway maintains the silencing for more than 20 generations.
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