Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila
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 Panor...
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eLife Sciences Publications Ltd
2021-02-01
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Online Access: | https://elifesciences.org/articles/65557 |
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author | Evelyn L Eastwood Kayla A Jara Susanne Bornelöv Marzia Munafò Vasileios Frantzis Emma Kneuss Elisar J Barbar Benjamin Czech Gregory J Hannon |
author_facet | Evelyn L Eastwood Kayla A Jara Susanne Bornelöv Marzia Munafò Vasileios Frantzis Emma Kneuss Elisar J Barbar Benjamin Czech Gregory J Hannon |
author_sort | Evelyn L Eastwood |
collection | DOAJ |
description | 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. |
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issn | 2050-084X |
language | English |
last_indexed | 2024-04-12T12:02:41Z |
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spelling | doaj.art-8c72a5d9b9b2465db0cee631acd9807f2022-12-22T03:33:48ZengeLife Sciences Publications LtdeLife2050-084X2021-02-011010.7554/eLife.65557Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in DrosophilaEvelyn L Eastwood0https://orcid.org/0000-0002-3932-0402Kayla A Jara1https://orcid.org/0000-0003-0406-2957Susanne Bornelöv2https://orcid.org/0000-0001-9276-9981Marzia Munafò3https://orcid.org/0000-0002-2689-8432Vasileios Frantzis4https://orcid.org/0000-0002-3497-700XEmma Kneuss5https://orcid.org/0000-0003-0662-8539Elisar J Barbar6https://orcid.org/0000-0003-4892-5259Benjamin Czech7https://orcid.org/0000-0001-8471-0007Gregory J Hannon8https://orcid.org/0000-0003-4021-3898Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United KingdomDepartment of Biochemistry and Biophysics, Oregon State University, Corvallis, United StatesCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United KingdomCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United KingdomCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United KingdomCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United KingdomDepartment of Biochemistry and Biophysics, Oregon State University, Corvallis, United StatesCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United KingdomCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United KingdomIn 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.https://elifesciences.org/articles/65557piRNA pathwayco-transcriptional silencingtransposonheterochromatindimerisationLC8 |
spellingShingle | Evelyn L Eastwood Kayla A Jara Susanne Bornelöv Marzia Munafò Vasileios Frantzis Emma Kneuss Elisar J Barbar Benjamin Czech Gregory J Hannon Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila eLife piRNA pathway co-transcriptional silencing transposon heterochromatin dimerisation LC8 |
title | Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila |
title_full | Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila |
title_fullStr | Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila |
title_full_unstemmed | Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila |
title_short | Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila |
title_sort | dimerisation of the picts complex via lc8 cut up drives co transcriptional transposon silencing in drosophila |
topic | piRNA pathway co-transcriptional silencing transposon heterochromatin dimerisation LC8 |
url | https://elifesciences.org/articles/65557 |
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