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Published July 1, 2014 | Published + Supplemental Material
Journal Article Open

piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells

Abstract

Transposable elements (TEs) occupy a large fraction of metazoan genomes and pose a constant threat to genomic integrity. This threat is particularly critical in germ cells, as changes in the genome that are induced by TEs will be transmitted to the next generation. Small noncoding piwi-interacting RNAs (piRNAs) recognize and silence a diverse set of TEs in germ cells. In mice, piRNA-guided transposon repression correlates with establishment of CpG DNA methylation on their sequences, yet the mechanism and the spectrum of genomic targets of piRNA silencing are unknown. Here we show that in addition to DNA methylation, the piRNA pathway is required to maintain a high level of the repressive H3K9me3 histone modification on long interspersed nuclear elements (LINEs) in germ cells. piRNA-dependent chromatin repression targets exclusively full-length elements of actively transposing LINE families, demonstrating the remarkable ability of the piRNA pathway to recognize active elements among the large number of genomic transposon fragments.

Additional Information

© 2014 Pezic et al.; Published by Cold Spring Harbor Laboratory Press. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. Published online June 17, 2014 in advance of the print journal; received March 3, 2014; revised version accepted May 28, 2014. We thank Katalin Fejes Tóth and members of the Aravin laboratory for helpful discussion and comments on the manuscript. We thank Rochelle Diamond and Diana Perez (California Institute of Technology) for invaluable help with cell sorting. We thank Alyssa Maskell (California Institute of Technology) for assistance with mouse work.We thank the Baltimore laboratory (California Institute of Technology) for lending us their magnetic cell-sorting equipment. We thank Sailakshmi Subramanian (Mount Sinai), Stijn van Dongen (EMBL-EBI), Georgi Marinov, Henry Amrhein, and Diane Trout (all California Institute of Technology) for help with bioinformatic and statistical analysis, and Igor Antoshechkin (California Institute of Technology) for help with RNA-seq. This work was supported by grants from the National Institutes of Health (R00 HD057233, R01 GM097363, and DP2 OD007371A), the Searle Scholar Award, and the Packard Fellowship to A.A.A.

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August 22, 2023
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