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
中科院分区:
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
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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DOI:
10.1073/pnas.1113310108
发表时间:
2011-12-06
影响因子:
11.1
作者:
Burton, Nick O.;Burkhart, Kirk B.;Kennedy, Scott
通讯作者:
Kennedy, Scott
影响因子:
4.5
作者:
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通讯作者:
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影响因子:
64.5
作者:
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通讯作者:
Moazed, Danesh
影响因子:
56.9
作者:
Grishok, A;Tabara, H;Mello, CC
通讯作者:
Mello, CC
影响因子:
64.5
作者:
Brennecke, Julius;Aravin, Alexei A.;Hannon, Gregory J.
通讯作者:
Hannon, Gregory J.