Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state
Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state
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DOI：
10.1101/gad.209841.112
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发表时间：
2013-02-15
影响因子：
10.5
通讯作者：
Toth, Katalin Fejes
中科院分区：
文献类型：
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作者：
Le Thomas, Adrien;Rogers, Alicia K.;Toth, Katalin Fejes
在后生动物生殖系中，piwi蛋白和相关的piwi相互作用RNA（piRNA）提供针对转座因子表达的防御系统。在细胞质中，皮尔纳序列引导piwi复合物通过内切核酸裂解破坏互补转座子转录物。然而，一些piwi家族成员是核的，这提高了piRNA介导的基因表达调控的替代途径的可能性。我们发现，果蝇Piwi被招募到染色质，共定位与RNA聚合酶II（Pol II）的多线染色体。Piwi在种系中的敲低增加了piRNA靶向的转座因子的表达，而蛋白质编码基因在很大程度上不受影响。Piwi耗尽后转座子的去阻遏与Pol II在其启动子上的占用增加相关。靶向报告基因构建体的piRNA的表达导致Pol II占据率的降低以及报告基因座上的抑制性H3K9me3标记和异染色质蛋白I（HP 1）的增加。我们的研究结果表明，Piwi识别与相关皮尔纳互补的靶标，并在发现正确靶标时通过建立抑制性染色质状态来诱导转录抑制。
In the metazoan germline, piwi proteins and associated piwi-interacting RNAs (piRNAs) provide a defense system against the expression of transposable elements. In the cytoplasm, piRNA sequences guide piwi complexes to destroy complementary transposon transcripts by endonucleolytic cleavage. However, some piwi family members are nuclear, raising the possibility of alternative pathways for piRNA-mediated regulation of gene expression. We found that Drosophila Piwi is recruited to chromatin, colocalizing with RNA polymerase II (Pol II) on polytene chromosomes. Knockdown of Piwi in the germline increases expression of transposable elements that are targeted by piRNAs, whereas protein-coding genes remain largely unaffected. Derepression of transposons upon Piwi depletion correlates with increased occupancy of Pol II on their promoters. Expression of piRNAs that target a reporter construct results in a decrease in Pol II occupancy and an increase in repressive H3K9me3 marks and heterochromatin protein 1 (HP1) on the reporter locus. Our results indicate that Piwi identifies targets complementary to the associated piRNA and induces transcriptional repression by establishing a repressive chromatin state when correct targets are found.