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MIWI 2 targets RNAs transcribed from pi RNA ‐dependent regions to drive DNA methylation in mouse prospermatogonia
Author(s) -
Watanabe Toshiaki,
Cui Xiekui,
Yuan Zhongyu,
Qi Hongying,
Lin Haifan
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201695329
Subject(s) - piwi interacting rna , argonaute , biology , dna methylation , rna , epigenetics , genetics , methylation , dna , chromatin , retrotransposon , microbiology and biotechnology , transposable element , gene , rna interference , gene expression , genome
Argonaute/Piwi proteins can regulate gene expression via RNA degradation and translational regulation using small RNA s as guides. They also promote the establishment of suppressive epigenetic marks on repeat sequences in diverse organisms. In mice, the nuclear Piwi protein MIWI 2 and Piwi‐interacting RNA s (pi RNA s) are required for DNA methylation of retrotransposon sequences and some other sequences. However, its underlying molecular mechanisms remain unclear. Here, we show that pi RNA ‐dependent regions are transcribed at the stage when pi RNA ‐mediated DNA methylation takes place. MIWI 2 specifically interacts with RNA s from these regions. In addition, we generated mice with deletion of a retrotransposon sequence either in a representative pi RNA ‐dependent region or in a pi RNA cluster. Both deleted regions were required for the establishment of DNA methylation of the pi RNA ‐dependent region, indicating that pi RNA s determine the target specificity of MIWI 2‐mediated DNA methylation. Our results indicate that MIWI 2 affects the chromatin state through base‐pairing between pi RNA s and nascent RNA s, as observed in other organisms possessing small RNA ‐mediated epigenetic regulation.