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425 results on '"Allshire, Robin C."'

1. C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line

Author

Zoch, Ansgar, Konieczny, Gabriela, Auchynnikava, Tania, Stallmeyer, Birgit, Rotte, Nadja, Heep, Madeleine, Berrens, Rebecca V., Schito, Martina, Kabayama, Yuka, Schöpp, Theresa, Kliesch, Sabine, Houston, Brendan, Nagirnaja, Liina, O’Bryan, Moira K., Aston, Kenneth I., Conrad, Donald F., Rappsilber, Juri, Allshire, Robin C., Cook, Atlanta G., Tüttelmann, Frank, and O’Carroll, Dónal

Published
2024
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6. Epigenetic gene silencing by heterochromatin primes fungal resistance

Author

Torres-Garcia, Sito, Yaseen, Imtiyaz, Shukla, Manu, Audergon, Pauline N. C. B., White, Sharon A., Pidoux, Alison L., and Allshire, Robin C.

Subjects
Yeast fungi -- Genetic aspects -- Growth, Chromatin -- Properties, Gene silencing -- Observations, Caffeine -- Properties, Company growth, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Heterochromatin that depends on histone H3 lysine 9 methylation (H3K9me) renders embedded genes transcriptionally silent.sup.1-3. In the fission yeast Schizosaccharomyces pombe, H3K9me heterochromatin can be transmitted through cell division provided the counteracting demethylase Epe1 is absent.sup.4,5. Heterochromatin heritability might allow wild-type cells under certain conditions to acquire epimutations, which could influence phenotype through unstable gene silencing rather than DNA change.sup.6,7. Here we show that heterochromatin-dependent epimutants resistant to caffeine arise in fission yeast grown with threshold levels of caffeine. Isolates with unstable resistance have distinct heterochromatin islands with reduced expression of embedded genes, including some whose mutation confers caffeine resistance. Forced heterochromatin formation at implicated loci confirms that resistance results from heterochromatin-mediated silencing. Our analyses reveal that epigenetic processes promote phenotypic plasticity, letting wild-type cells adapt to unfavourable environments without genetic alteration. In some isolates, subsequent or coincident gene-amplification events augment resistance. Caffeine affects two anti-silencing factors: Epe1 is downregulated, reducing its chromatin association, and a shortened isoform of Mst2 histone acetyltransferase is expressed. Thus, heterochromatin-dependent epimutation provides a bet-hedging strategy allowing cells to adapt transiently to insults while remaining genetically wild type. Isolates with unstable caffeine resistance show cross-resistance to antifungal agents, suggesting that related heterochromatin-dependent processes may contribute to resistance of plant and human fungal pathogens to such agents. Fission yeast grown in sublethal levels of caffeine develop heterochromatin-dependent epimutations conferring unstable heritable gene silencing that conveys resistance to caffeine, while remaining genetically wild type., Author(s): Sito Torres-Garcia [sup.1] , Imtiyaz Yaseen [sup.1] , Manu Shukla [sup.1] , Pauline N. C. B. Audergon [sup.1] [sup.2] , Sharon A. White [sup.1] , Alison L. Pidoux [sup.1] [...]

Published
2020
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8. Gain-of-function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of Polycomb-regulated regions

Author

Heyn, Patricia, Logan, Clare V., Fluteau, Adeline, Challis, Rachel C., Auchynnikava, Tatsiana, Martin, Carol-Anne, Marsh, Joseph A., Taglini, Francesca, Kilanowski, Fiona, Parry, David A., Cormier-Daire, Valerie, Fong, Chin-To, Gibson, Kate, Hwa, Vivian, Ibáñez, Lourdes, Robertson, Stephen P., Sebastiani, Giorgia, Rappsilber, Juri, Allshire, Robin C., Reijns, Martin A. M., Dauber, Andrew, Sproul, Duncan, and Jackson, Andrew P.

Published
2019
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12. Two-factor authentication underpins the precision of the piRNA pathway

Author

Dias Mirandela, Madeleine, Zoch, Ansgar, Leismann, Jessica, Webb, Shaun, Berrens, Rebecca V., Valsakumar, Devisree, Kabayama, Yuka, Auchynnikava, Tania, Schito, Martina, Chowdhury, Tamoghna, MacLeod, David, Xiang, Xinyu, Zou, Juan, Rappsilber, Juri, Allshire, Robin C., Voigt, Philipp, Cook, Atlanta G., Barau, Joan, and O’Carroll, Dónal

Abstract

The PIWI-interacting RNA (piRNA) pathway guides the DNA methylation of young, active transposons during germline development in male mice1. piRNAs tether the PIWI protein MIWI2 (PIWIL4) to the nascent transposon transcript, resulting in DNA methylation through SPOCD1 (refs. 2–5). Transposon methylation requires great precision: every copy needs to be methylated but off-target methylation must be avoided. However, the underlying mechanisms that ensure this precision remain unknown. Here, we show that SPOCD1 interacts directly with SPIN1 (SPINDLIN1), a chromatin reader that primarily binds to H3K4me3-K9me3 (ref. 6). The prevailing assumption is that all the molecular events required for piRNA-directed DNA methylation occur after the engagement of MIWI2. We find that SPIN1 expression precedes that of both SPOCD1 and MIWI2. Furthermore, we demonstrate that young LINE1 copies, but not old ones, are marked by H3K4me3, H3K9me3 and SPIN1 before the initiation of piRNA-directed DNA methylation. We generated a Spocd1separation-of-function allele in the mouse that encodes a SPOCD1 variant that no longer interacts with SPIN1. We found that the interaction between SPOCD1 and SPIN1 is essential for spermatogenesis and piRNA-directed DNA methylation of young LINE1 elements. We propose that piRNA-directed LINE1 DNA methylation requires a developmentally timed two-factor authentication process. The first authentication is the recruitment of SPIN1–SPOCD1 to the young LINE1 promoter, and the second is MIWI2 engagement with the nascent transcript. In summary, independent authentication events underpin the precision of piRNA-directed LINE1 DNA methylation.

Published
2024
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16. The SPARC complex defines RNAPII promoters in Trypanosoma brucei

Author

Staneva, Desislava P, primary, Bresson, Stefan, additional, Auchynnikava, Tatsiana, additional, Spanos, Christos, additional, Rappsilber, Juri, additional, Jeyaprakash, A Arockia, additional, Tollervey, David, additional, Matthews, Keith R, additional, and Allshire, Robin C, additional

Published
2022
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19. RNAi-Mediated Chromatin Silencing in Fission Yeast

Author

White, Sharon A., Allshire, Robin C., Compans, Richard W., editor, Cooper, Max D., editor, Honjo, Tasuku, editor, Koprowski, Hilary, editor, Melchers, Fritz, editor, Oldstone, Michael B. A., editor, Olsnes, Sjur, editor, Vogt, Peter K., editor, and Paddison, Patrick J., editor

Published
2008
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21. The SPARC complex defines RNAPII promoters in Trypanosoma brucei

Author

Staneva, Desislava P., primary, Bresson, Stefan, additional, Auchynnikava, Tatsiana, additional, Spanos, Christos, additional, Rappsilber, Juri, additional, Jeyaprakash, A. Arockia, additional, Tollervey, David, additional, Matthews, Keith R., additional, and Allshire, Robin C., additional

Published
2022
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25. Proteasome-dependent truncation of the negative heterochromatin regulator Epe1 mediates antifungal resistance

Author

Yaseen, Imtiyaz, primary, White, Sharon A., additional, Torres-Garcia, Sito, additional, Spanos, Christos, additional, Lafos, Marcel, additional, Gaberdiel, Elisabeth, additional, Yeboah, Rebecca, additional, Karoui, Meriem El, additional, Rappsilber, Juri, additional, Pidoux, Alison L., additional, and Allshire, Robin C., additional

Published
2021
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28. iNucs: inter-nucleosome interactions

Author

Oveisi, Mehrdad, primary, Shukla, Manu, additional, Seymen, Nogayhan, additional, Ohno, Masae, additional, Taniguchi, Yuichi, additional, Nahata, Sunil, additional, Loos, Remco, additional, Mufti, Ghulam J, additional, Allshire, Robin C, additional, Dimitrov, Stefan, additional, and Karimi, Mohammad M, additional

Published
2021
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34. SPOCD1 is an essential executor of piRNA-directed 1 de novo DNA methylation

Author

Zoch, Ansgar, Auchynnikava, Tania, Berrens, Rebecca V., Kabayama, Yuka, Schöpp, Theresa, Heep, Madeleine, Vasiliauskaitė, Lina, Pérez-Rico, Yuvia A, Cook, Atlanta G., Shkumatava, Alena, Rappsilber, Juri, Allshire, Robin C., and O'Carroll, Donal

Subjects
endocrine system, urogenital system
Abstract

In mammals, the acquisition of the germline from the soma provides the germline with an essential challenge, the necessity to erase and reset genomic methylation. In the malegermline RNA-directed DNA methylation silences young active transposable elements(TEs)2-4. The PIWI protein MIWI2 (PIWIL4) and its associated PIWI-interacting RNAs(piRNAs) instruct TE DNA methylation. PiRNAs are proposed to tether MIWI2 tonascent TE transcripts, however the mechanism by which MIWI2 directs de novo TEmethylation is poorly understood but central to the immortality of the germline. Here, we define the interactome of MIWI2 in foetal gonocytes that are undergoing de novo genome methylation and identify a novel MIWI2-associated factor, SPOCD1, that is essential for young TE methylation and silencing. The loss of Spocd1 in mice results in male-specific infertility but impacts neither piRNA biogenesis nor localization of MIWI2 to the nucleus. SPOCD1 is a nuclear protein and its expression is restricted to the period of de novogenome methylation. We found SPOCD1 co-purified in vivo with DNMT3L and DNMT3A, components of the de novo methylation machinery as well as constituents of the NURD and BAF chromatin remodelling complexes. We propose a model where by tethering of MIWI2 to a nascent TE transcript recruits repressive chromatin remodelling activities and the de novo methylation apparatus through SPOCD1. In summary, we have identified a novel and essential executor of mammalian piRNA-directed DNA methylation.

Published
2020

36. RNA Pol II subunit Rpb7 promotes centromeric transcription and RNAi-directed chromatin silencing

Author

Djupedal, Ingela, Portoso, Manuela, Spahr, Henrik, Binilla, Carolina, Gustafsson, Claes M., Allshire, Robin C., and Ekwall, Karl

Subjects
Centromeres -- Research, Chromatin -- Research, Biological sciences
Abstract

The study shows that another Pol II subunit, Rbp7 has a specific role in pre-small interfering RNA (siRNA) transcription. In contrast to other Pol II subunits, Rpb7 promotes pre-siRNA transcription required for RNAinterference-directed chromatin silencing.

Published
2005

37. SpEDIT: A fast and efficient CRISPR/Cas9 method for fission yeast

Author

Torres-Garcia, Sito, primary, Di Pompeo, Lorenza, additional, Eivers, Luke, additional, Gaborieau, Baptiste, additional, White, Sharon A., additional, Pidoux, Alison L., additional, Kanigowska, Paulina, additional, Yaseen, Imtiyaz, additional, Cai, Yizhi, additional, and Allshire, Robin C., additional

Published
2020
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41. Fission yeast CENP-B homologs nucleate centromeric heterochromatin by promoting heterochromatin-specific histone tail modifications

Author

Nakagawa, Hiromi, Lee, Joon-Kyu, Hurwitz, Jerard, Allshire, Robin C., Nakayama, Jun-ichi, Grewal, Shiv I. S., Tanaka, Katsunori, and Murakami, Yota

Subjects
Genetic research -- Analysis, Chromatin -- Genetic aspects, Yeast -- Genetic aspects, Nucleation -- Physiological aspects, Histones -- Genetic aspects, Methylation -- Physiological aspects, Biological sciences
Abstract

Research has been conducted on heterochromatin. Results indicate that CENP-B homologs recruit heterochromatin protein Swi6 to centromeric heterochromatin via histone deacetylation or methylation in centromeric heterochromatin.

Published
2002

43. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain

Author

Bannister, Andrew J., Zegerman, Philip, Partridge, Janet F., Miska, Eric A., Thomas, Jean O., Allshire, Robin C., and Kouzarides, Tony

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Andrew J. Bannister [1, 2]; Philip Zegerman [1, 2]; Janet F. Partridge [3]; Eric A. Miska [1]; Jean O. Thomas [4]; Robin C. Allshire [3]; Tony Kouzarides (corresponding author) [...]

Published
2001
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50. Centromere DNA destabilizes H3 nucleosomes to promote CENP-A deposition during the cell cycle

Author

Shukla, Manu, Tong, Pin, White, Sharon A., Singh, Puneet P., Reid, Angus M., Catania, Sandra, Pidoux, Alison L., and Allshire, Robin C.

Subjects
DNA Replication, S. pombe, Chromosomal Proteins, Non-Histone, Centromere, nucleosome, macromolecular substances, fission yeast, Article, Chromatin, Nucleosomes, S Phase, kinetochore, centromere, cell cycle, chromosome, RNAPII, transcription, CENP-A, Centromere Protein A
Abstract

Summary Active centromeres are defined by the presence of nucleosomes containing CENP-A, a histone H3 variant, which alone is sufficient to direct kinetochore assembly. Once assembled at a location, CENP-A chromatin and kinetochores are maintained at that location through a positive feedback loop where kinetochore proteins recruited by CENP-A promote deposition of new CENP-A following replication. Although CENP-A chromatin itself is a heritable entity, it is normally associated with specific sequences. Intrinsic properties of centromeric DNA may favor the assembly of CENP-A rather than H3 nucleosomes. Here we investigate histone dynamics on centromere DNA. We show that during S phase, histone H3 is deposited as a placeholder at fission yeast centromeres and is subsequently evicted in G2, when we detect deposition of the majority of new CENP-ACnp1. We also find that centromere DNA has an innate property of driving high rates of turnover of H3-containing nucleosomes, resulting in low nucleosome occupancy. When placed at an ectopic chromosomal location in the absence of any CENP-ACnp1 assembly, centromere DNA appears to retain its ability to impose S phase deposition and G2 eviction of H3, suggesting that features within centromere DNA program H3 dynamics. Because RNA polymerase II (RNAPII) occupancy on this centromere DNA coincides with H3 eviction in G2, we propose a model in which RNAPII-coupled chromatin remodeling promotes replacement of H3 with CENP-ACnp1 nucleosomes., Highlights • Histone H3 levels increase at centromeres during S phase • New CENP-A replaces H3 during G2 • Centromere DNA drives H3 dynamics independent of centromere proteins • Eviction of H3 is coincident with recruitment of elongating RNAPII, Shukla et al. show that histone H3 is transiently deposited as a placeholder in centromeric chromatin during S phase and subsequently replaced by new centromere-specific CENP-ACnp1 during G2. Eviction of H3 coincides with RNAPII recruitment, suggesting that transcription-coupled events may be involved.

Published
2018

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