期刊
GENES & DEVELOPMENT
卷 27, 期 4, 页码 390-399出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.209841.112
关键词
piRNA; Piwi; chromatin; RNA polymerase II; transcription; transposon
资金
- Gordon Ross Medical Foundation
- Beckman Foundation
- Donald Bren Endowment
- NIH [U54 HG004576]
- National Institutes of Health [R01 GM097363, R00 HD057233, DP2 OD007371A]
- Searle Scholar Award
- Ellison Medical Foundation New Scholar in Aging Award
- [NIH/NRSA 5T32 GM07616]
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.
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