Pezic Dubravka, Manakov Sergei A, Sachidanandam Ravi, Aravin Alexei A
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA;
Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA.
Genes Dev. 2014 Jul 1;28(13):1410-28. doi: 10.1101/gad.240895.114. Epub 2014 Jun 17.
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.
转座元件（TEs）占据了后生动物基因组的很大一部分，对基因组完整性构成持续威胁。这种威胁在生殖细胞中尤为关键，因为转座元件诱导的基因组变化会传递给下一代。小的非编码piwi相互作用RNA（piRNAs）识别并沉默生殖细胞中多种转座元件。在小鼠中，piRNA引导的转座子抑制与其序列上CpG DNA甲基化的建立相关，但piRNA沉默的机制和基因组靶点范围尚不清楚。在这里，我们表明，除了DNA甲基化外，piRNA途径对于维持生殖细胞中长散在核元件（LINEs）上高水平的抑制性组蛋白修饰H3K9me3也是必需的。piRNA依赖的染色质抑制专门针对活跃转座的LINE家族的全长元件，这表明piRNA途径具有非凡的能力，能够在大量基因组转座子片段中识别活跃元件。
