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Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila

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In animal gonads, the PIWI-interacting RNA (piRNA) pathway guards genome integrity in part through the co-transcriptional gene silencing of transposon insertions. In Drosophila ovaries, piRNA-loaded Piwi detects nascent transposon transcripts and instructs heterochromatin formation through the Panoramix-induced co-transcriptional silencing (PICTS) complex, containing Panoramix, Nxf2 and Nxt1. Here, we report that the highly conserved dynein light chain LC8/Cut-up (Ctp) is an essential component of the PICTS complex. Loss of Ctp results in transposon de-repression and a reduction in repressive chromatin marks specifically at transposon loci. In turn, Ctp can enforce transcriptional silencing when artificially recruited to RNA and DNA reporters. We show that Ctp drives dimerisation of the PICTS complex through its interaction with conserved motifs within Panoramix. Artificial dimerisation of Panoramix bypasses the necessity for its interaction with Ctp, demonstrating that conscription of a protein from a ubiquitous cellular machinery has fulfilled a fundamental requirement for a transposon silencing complex.



Research Article, Chromosomes and Gene Expression, piRNA pathway, co-transcriptional silencing, transposon, heterochromatin, dimerisation, LC8, D. melanogaster

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eLife Sciences Publications, Ltd
Cancer Research UK (Core funding (A21143))
Wellcome Trust (Investigator award (110161/Z/15/Z))
National Science Foundation (Award 1617019)
Royal Society (Wolfson Research Professor (RP130039))
Boehringer Ingelheim Fonds (PhD fellowship)