Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state

被引:377
作者
Le Thomas, Adrien [1 ,2 ]
Rogers, Alicia K. [1 ]
Webster, Alexandre [1 ]
Marinov, Georgi K. [1 ]
Liao, Susan E. [1 ]
Perkins, Edward M. [1 ]
Hur, Junho K. [1 ]
Aravin, Alexei A. [1 ]
Toth, Katalin Fejes [1 ]
机构
[1] CALTECH, Pasadena, CA 91125 USA
[2] Univ Paris 06, Ecole Doctorale Complex Vivant, F-75005 Paris, France
基金
美国国家卫生研究院;
关键词
piRNA; Piwi; chromatin; RNA polymerase II; transcription; transposon; DROSOPHILA SOMATIC-CELLS; LARGE GENE LISTS; DNA METHYLATION; ARGONAUTE PROTEINS; IN-VIVO; HETEROCHROMATIN FORMATION; LYSINE-9; METHYLATION; EPIGENETIC MEMORY; MESSENGER-RNAS; C; ELEGANS;
D O I
10.1101/gad.209841.112
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:390 / 399
页数:10
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