Allshire Lab

EPIGENETICS & SPECIALIZED CHROMATIN

Genomes are packaged as chromatin in nucleosomes composed of core histones (H2A/H2B/H3/H4). Epigenetic processes, mediated by histone post-translational modifications, allow continued gene expression/repression in cell lineages. Understanding how such ‘marks’ establish and propagate chromatin states is critical for specifying and maintaining distinct cell types. Moreover, epigenetic states provide a source of phenotypic variation, independent of DNA sequence.

Lineage commitment and reprogramming of cell fate involves both chromatin-mediated shutdown and activation of elaborate transcription programmes. Specialised chromatin domains are therefore fundamentally important, but dissecting these epigenetic mechanisms remains challenging in mammals. Model organisms such as fission yeast are effective for uncovering important principles applicable across phyla.

Epigenetic heritability is an important property of both heterochromatin and CENP-A chromatin: once formed they can persist without initiating signals. Since debilitating disorders (i.e. Friedreich’s Ataxia, FSHD) result from aberrant heterochromatin-mediated gene silencing, it is important to understand events that promote and deter gene silencing. Moreover, stochastic gene silencing in response to environmental cues may trigger transgenerational inheritance of epigenetically-regulated traits. Functional CENP-A chromatin is assembled only at centromeres; chromosome missegregation and aneuploidy result from defective CENP-A and kinetochore assembly. Regulated CENP-A deposition prevents unstable chromosome formation by ensuring assembly of only one kinetochore per chromosome. Overexpression of CENP-A and its assembly factors is prevalent in various aggressive tumours where they may drive genome instability.

Our goal is to decipher conserved mechanisms that establish, maintain and regulate assembly of heterochromatin and CENP-A chromatin domains. We aim to provide provide insight into how heterochromatin forms on canonical pericentromere repeats. Heterochromatin may also silence genes throughout the genome, we are investigating how stochastic silencing might exert epigenetic influences on phenotype. We also strive to understand how heterochromatin, spatial nuclear organisation and non-coding RNAPII transcription combine to mediate CENP-A incorporation at centromeres.

Trypanosome epigenetics: in collaboration with Keith Matthews we are investigating the nature and function of heterochromatin in the sleeping sickness parasite, Trypanosoma brucei.

GROUP MEMBERS

Professor of Chromosome Biology

B.A. Genetics: Trinity College Dublin. 1981.
Ph.D. MRC Mammalian Genome Unit, University of Edinburgh. 1985. Royal Commission for the Exhibition of 1851 PhD Scholarship.
Postdoc: MRC Human Genetics Unit, Edinburgh. 1985-1989.
Visiting Scientist - Cold Spring Harbor Laboratories, New York. 1989-1990.
Junior Group Leader: MRC Human Genetics Unit, Edinburgh 1990-1995.
Senior Scientist: MRC Human Gentics Unit, Edinburgh. 1995-2002.
Wellcome Trust Principal Research Fellow, Wellcome Centre for Cell Biology, University of Edinburgh. 2002-present.
EMBO Member. 1998.
Fellow of the Royal Society of Edinburgh - 2005.
Fellow of the Royal Society, London - 2011.
Genetics Society (UK) Medal - 2013.
Fellow of the Academy of Medical Sciences, London 2020.

Alison Pidoux

Sharon White

Manu Shukla

Pin Tong

Andreas Fellas

CONTACT us

Discovery Research Platform for Hidden Cell Biology
Institute of Cell Biology
School of Biological Sciences
University of Edinburgh
6.34 Michael Swann Building
Max Born Crescent
Edinburgh EH9 3BF
Scotland - UK

Tel: +44 131 650 7103

Find US:

The Wellcome Centre for Cell Biology is located in the Michael Swann Building (tall light cream/green building on the King's Buildings Campus, ~4 km south of the city centre. The Michael Swann Building is the third building, approximately 100m, on the left through Entrance 4 from Mayfield Road and can be reached from the city centre by bus or taxi.

Taxi: fare from Edinburgh airport is ~£25 GBP and from Edinburgh city centre ~£10 GBP, depending on the traffic conditions.

Tram: Edinburgh Tram leaves approximately every 10 minutes from Edinburgh Airport and takes 35 minutes to Edinburgh City Centre (Princes Street). Tickets: £5 (single) £8 (return) - buy online using the Lothian Buses m-tickets App: lothianbuses.com/apps

Bus: Lothian Buses provide an express Airlink service to/from Edinburgh Airport to the city centre and operate a network of buses around the city. Services 42 and 67 leave from the City Centre/Princes Street and stop close to Kings Buildings on Mayfield Road. Other services such as the 3, 7, 8, 29, 30, 31, 37, 47 leave from the city centre and stop at Cameron Toll which is approximately 10 minutes walk away from the Wellcome Centre for Cell Biology.

By Air: There are regular direct flights to Edinburgh from London, Amsterdam, Barcelona, Frankfurt, Paris and other European cities. There are direct flights from New York (Newark - Continental; JFK - Delta). For more information see Edinburgh Airport. Edinburgh is only 50 miles from Glasgow and Glasgow Airport.

By Train: There are excellent train services Edinburgh-Glasgow and Edinburgh-London Kings Cross.

Interested In joining us?

Post-Doctoral Researcher and Ph.D. student applications from UK, EU, US & Overseas are always considered.

Various Post-doctoral funding sources can be explored:

Post-Doc fellowships: EMBO, FEBS, HFSP, Newton, Marie Curie, Wellcome.

Please send your CV and summary of your research interests to: robin.allshire@ed.ac.uk

PhD Student Opportunities:

Darwin Trust - darwintrust.bio.ed.ac.uk/edinburgh (but you must email me before applying - Deadline 19th Jan 2022), Edinburgh Global, Principal's Career Development, EastBio, Precision Medicine, Boehringer Ingelheim Fonds,

Wellcome Four Year PhD Programme in Integrative Cell Mechanisms. Deadline 6th December 2021.

Please send your CV and summary of your research interests to: robin.allshire@ed.ac.uk

Possible PhD Student Project to start 2023 - collaboration with Ramon Grima

Quantifying and Modelling Mechanisms of Antifungal Resistant Epimutation Epimutation and Heritability

Fungal survival in harsh environments involves stress-sensing pathways that reprogram their proteomes. New conditions, including climate change, can push opportunistic fungi to colonise novel niches, potentially becoming harmful pathogens. Effective antifungal/fungicide treatments are limited in number precisely because fungi are adept at resisting challenges. Antifungal resistance is increasingly prevalent, raising fungal-borne disease frequencies in humans and crops [1,2]. Conventional wisdom that resistance results solely from genetic mutations was overturned by our discovery that external insults selects cells with a distinct epigenetic landscape - repressive heterochromatin over various genes whose reduced expression confers resistance (e.g. mitochondrial proteins) [3,4]. Such heterochromatin-dependent ‘epimutations’ are unstable, slowly losing resistance upon external insult removal. By combining genetic, genomic, transcriptomic, proteomic, metabolomic, bioinformatic and mathematical analyses we aim to provide a comprehensive understanding of the regulatory mechanisms utilized by cells that successfully display resistance. We hypothesize that extracellular stresses, including fungicides widely used in agriculture, reprogramme fungal epigenomes so that they transiently acquire heterochromatin at locations which confer heritable, but unstable, resistance.

This project will combine the power of classic Luria-Delbruck fluctuation tests with low cell number/single cell (ATAC-seq, Cut&Tag and RNA-seq) sequencing workflows [5], to dissect the events that result in the emergence of transiently antifungal/fungicide resistant lineages due to epimutation formation. The frequency and heritability of such epimutations will be measured and will be used to estimate the frequency of switching events between various pre-existing and selected cell states by means of recently developed moment-based inference techniques [6].

Experiments will use 96-well plate-based single cell lineage fluctuation tests designed to measure the frequency of epimutant formation in wild-type and manipulated cells. These assay will also identify enriched epimutant bearing lineages. We will explore the possibility of using microfluidics platforms to conduct larger scale (1000’s) real time lineage analyses, identification and collection. HTP sequencing approaches will be applied (ATAC-seq, Cut&Tag and RNA-seq) with associated bioinformatics to characterise changes in the epigenome landscape and gene expression in such lineages. Single cell sequencing approaches will be employed to identify signature transcriptional and epigenomic landscapes which define epimutant states before and after resistant lineage emergence. Additionally, fluorescent reporters informed by these fluctuation assays, are expected to allow the enrichment of such cells by FACS or microfluidics to allow deeper characterisation of epimutant states. The student will utilize custom-written code implementing a moment-based inference algorithm that estimates the frequency of switching events from fluctuation test measurements6. Training will be provided on stochastic modelling and inference techniques.

The project will involve collaboration with Abhyudai Singh (University of Delaware; [5]) and the student will have the opportunity to develop single cell sequence analysis skills in collaboration with Maria Colome-Tatche (LMU Munich;[7]) ) through the EpiCrossBorders scheme: www.helmholtzresearchschool-epigenetics.org

Successful applicants will have the opportunity to become proficient in variety of associated bioinformatics and computational biology. During the course of this project the appointed student will develop their data analyses, statistical, presentation, critical thinking and report writing skills.

1. Fisher MC, Hawkins NJ, Sanglard D. & Gurr SJ. Worldwide emergence of resistance to antifungal drugs challenges human health and food security. Science 360, 739–742 (2018).

2. Fisher MC, Gurr SJ, Cuomo CA, Blehert DS, Jin H, Stukenbrock EH, Stajich JE, Kahmann R, Boone C, Denning DW, Gow NAR, Klein BS, Kronstad JW, Sheppard DC, Taylor JW, Wright GD, Heitman J, Casadevall A, Cowen LE. Threats posed by the fungal kingdom to humans, wildlife, and agriculture. mBio 11, e00449-20 (2020).

3. Torres-Garcia S, Yaseen I, Shukla M, Audergon PNCB, White SA, Pidoux AL, Allshire RC. Epigenetic gene silencing by heterochromatin primes fungal resistance. Nature 585, 453–458 (2020).

4. YYaseen I, White SA, Torres-Garcia S, Spanos C, Lafos M, Gaberdiel E, Yeboah R, El Karoui M, Rappsilber J, Pidoux AL, Allshire RC. Proteasome-dependent truncation of the negative heterochromatin regulator Epe1 mediates antifungal resistance. Nat Struct Mol Biol. 29, 745-758. doi: 10.1038/s41594-022-00801-y (2022).

5. Shaffer SM, Emert BL, Reyes Hueros RA, Cote C, Harmange G, Schaff DL, Sizemore AE, Gupte R, Torre E, Singh A, Bassett DS, Raj A. Memory Sequencing Reveals Heritable Single-Cell Gene Expression Programs Associated with Distinct Cellular Behaviors. Cell 182, 947-959 (2020.

6. Cao Z, Grima R. Accuracy of parameter estimation for auto-regulatory transcriptional feedback loops from noisy data. J R Soc Interface 16, 20180967 doi: 10.1098/rsif.2018.0967 (2019).

7. Danese A, Richter ML, Chaichoompu K, Fischer DS, Theis FJ, Colomé-Tatché M. EpiScanpy: integrated single-cell epigenomic analysis. Nature Commun. 12, 5228 doi: 10.1038/s41467-021-25131-3 (2021).

SpEDIT

To see what you can do using our system, please read the SpEDIT Paper

To download required instructions and sequences, please visit the SpEDIT Drive

For additional information or reagent request, please contact: Sito Torres-Garcia - sito.torres@ed.ac.uk, Robin Allshire - robin.allshire@ed.ac.uk

PUBLICATIONS

Previous releases:

The SPARC complex defines RNAPII promoters in Trypanosoma brucei. (2022) Staneva DP, Bresson S, Auchynnikava T, Spanos C, Rappsilber J, Jeyaprakash AA, Tollervey D, Matthews KR, Allshire RC. eLife 11:e83135. doi: 10.7554/eLife.83135.

Proteasome-dependent truncation of the negative heterochromatin regulator Epe1 mediates antifungal resistance. (2022) Yaseen I, White SA, Torres-Garcia S, Spanos C, Lafos M, Gaberdiel E, Yeboah R, El Karoui M, Rappsilber J, Pidoux AL, Allshire RC. Nat Struct Mol Biol. 8:745-758. doi: 10.1038/s41594-022-00801-y.

Establishment of centromere identity is dependent on nuclear spatial organization. (2022) Wu W, McHugh T, Kelly DA, Pidoux AL, Allshire RC. Curr Biol.32:3121. doi:10.1016/j.cub.2022.06.048

iNucs: Inter-Nucleosome Interactions. (2021) Oveisi M, Shukla M, Seymen N, Ohno M, Taniguchi Y, Nahata S, Loos R, Mufti GJ, Allshire RC, Dimitrov S, Karimi MM. Bioinformatics. Oct 8;37(23):4562-3. doi: 10.1093/bioinformatics/btab698. Online ahead of print.

A systematic analysis of Trypanosoma brucei chromatin factors identifies novel protein interaction networks associated with sites of transcription initiation and termination. (2021) Staneva DP, Carloni R, Auchynnikava T, Tong P, Rappsilber J, Jeyaprakash AA, Matthews KR, Allshire RC.Genome Res. 2021 Nov;31(11):2138-2154. doi: 10.1101/gr.275368.121.

NANOS2 is a sequence-specific mRNA-binding protein that promotes transcript degradation in spermatogonial stem cells. (2021) Codino A, Turowski T, van de Lagemaat LN, Ivanova I, Tavosanis A, Much C, Auchynnikava T, Vasiliauskaitė L, Morgan M, Rappsilber J, Allshire RC, Kranc KR, Tollervey D, O'Carroll D.iScience. 24(7):102762. doi: 10.1016/j.isci.2021.102762. eCollection 2021 Jul 23.PMID: 34278268

SpEDIT: A fast and efficient CRISPR/Cas9 method for fission yeast. (2020) Torres-Garcia, S., Di Pompeo, L., Eivers, L., Gaborieau, B., White, S.A., Pidoux, A.L., Kanigowska, P., Yaseen, I., Cai, Y. & Allshire, R.C. Wellcome Open Res. 5:274.

Large domains of heterochromatin direct the formation of short mitotic chromosome loops. (2020) Fitz-James, M.H., Tong, P., Pidoux, A.L., Ozadam, H., Yang, L., White, S.A., Dekker, J. & Allshire, R.C. eLife. 9:e57212.

Epigenetic gene silencing by heterochromatin primes fungal resistance. (2020) Torres-Garcia, S., Yaseen, I., Shukla, M., Audergon, P.N.C.B., White, S.A., Pidoux, A.L. & Allshire, R.C. Nature. 585, 453–458.

TEX15 is an essential executor of MIWI2-directed transposon DNA methylation and silencing. (2020) Schöpp, T., Zoch, A., Berrens, R.V., Auchynnikava, T., Kabayama, Y., Vasiliauskaitė, L., Rappsilber, J., Allshire, R.C. & O'Carroll, D. Nat Commun. 11, 3739.

SPOCD1 is an essential executor of piRNA-directed de novo DNA methylation. (2020) Zoch, A., Auchynnikava, T., Berrens, R.V., Kabayama, Y., Schöpp, T., Heep, M., Vasiliauskaitė, L., Pérez-Rico, Y.A., Cook, A.G., Shkumatava, A., Rappsilber, J., Allshire, R.C. & O'Carroll, D. Nature. 584, 635–639.

Hap2-Ino80-facilitated transcription promotes de novo establishment of CENP-A chromatin. Singh, P.P., Shukla, M., White, S.A., Lafos, M., Tong, P., Auchynnikava, T., Spanos, C., Rappsilber, J., Pidoux, A.L. & Allshire, R.C. (2020). Genes & development. 34 (3-4), pp. 226–238. doi: 10.1101/gad.332536.119.

Fitness Landscape of the Fission Yeast Genome. Grech, L., Jeffares, D.C., Sadée, C.Y., Rodríguez-López, M., Bitton, D.A., Hoti, M., Biagosch, C., Aravani, D., Speekenbrink, M., Illingworth, C.J.R., Schiffer, P.H., Pidoux, A.L., Tong, P., Tallada, V.A., Allshire, R.C, Levin, H.L., Bähler, J. (2019). Claus Wilke (ed.). Molecular biology and evolution. 36 (8), pp. 1612–1623. https://doi.org/10.1093/molbev/msz113.

A programmed wave of uridylation-primed mRNA degradation is essential for meiotic progression and mammalian spermatogenesis. Morgan, M., Kabayama, Y., Much, C., Ivanova, I., Di Giacomo, M., Auchynnikava, T., Monahan, J.M., Vitsios, D.M., Vasiliauskaitė, L., Comazzetto, S., Rappsilber, J., Allshire, R.C., Porse, B.T., Enright, A.J., et al. (2019) . Cell research. 29 (3), pp. 221–232. https://doi.org/10.1038/s41422-018-0128-1.

Interspecies conservation of organisation and function between nonhomologous regional centromeres. Tong, P., Pidoux, A.L., Toda, N.R.T., Ard, R., Berger, H., Shukla, M., Torres-Garcia, J., Müller, C.A., Nieduszynski, C.A. & Allshire, R.C. (2019). Nature communications. 10 (1), pp. 2343. https://doi.org/10.1038/s41467-019-09824-4.

Centromere DNA Destabilizes H3 Nucleosomes to Promote CENP-A Deposition during the Cell Cycle. Shukla, M., Tong, P., White, S.A., Singh, P.P., Reid, A.M., Catania, S., Pidoux, A.L. & Allshire, R.C. Current Biology. 2018 Nov 29. doi:https://doi.org/10.1016/j.cub.2018.10.049. In press. Corrected Proof.

Gain-of-function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of Polycomb-regulated regions. Heyn P, Logan CV, Fluteau A, Challis RC, Auchynnikava T, Martin CA, Marsh JA, Taglini F, Kilanowski F, Parry DA, Cormier-Daire V, Fong CT, Gibson K, Hwa V, Ibáñez L, Robertson SP, Sebastiani G, Rappsilber J, Allshire RC, Reijns MAM, Dauber A, Sproul D, Jackson AP. Nat Genet. 2018 Nov 26. doi: 10.1038/s41588-018-0274-x. [Epub ahead of print].

Ten principles of heterochromatin formation and function. Allshire RC, Madhani HD. Nat Rev Mol Cell Biol. 2017 Dec 13. doi: 10.1038/nrm.2017.119. [Epub ahead of print] Review.

RNA polymerase II stalling at pre-mRNA splice sites is enforced by ubiquitination of the catalytic subunit. Milligan L, Sayou C, Tuck A, Auchynnikava T, Reid JE, Alexander R, Alves FL, Allshire R, Spanos C, Rappsilber J, Beggs JD, Kudla G, Tollervey D. Elife. 2017 Oct 13;6. pii: e27082. doi: 10.7554/eLife.27082.

Emerging Properties and Functional Consequences of Noncoding Transcription. Ard R, Allshire RC, Marquardt S. Genetics. 2017 Oct;207(2):357-367. doi: 10.1534/genetics.117.300095. Review.

Histone H3G34R mutation causes replication stress, homologous recombination defects and genomic instability in S. pombe.Yadav RK, Jablonowski CM, Fernandez AG, Lowe BR, Henry RA, Finkelstein D, Barnum KJ, Pidoux AL, Kuo YM, Huang J, O'Connell MJ, Andrews AJ, Onar-Thomas A, Allshire RC, Partridge JF. Elife. 2017 Jul 18;6. pii: e27406. doi: 10.7554/eLife.27406.

Transposon-driven transcription is a conserved feature of vertebrate spermatogenesis and transcript evolution. Davis MP, Carrieri C, Saini HK, van Dongen S, Leonardi T, Bussotti G, Monahan JM, Auchynnikava T, Bitetti A, Rappsilber J, Allshire RC, Shkumatava A, O'Carroll D, Enright AJ. EMBO Rep. 2017 Jul;18(7):1231-1247. doi: 10.15252/embr.201744059. Epub 2017 May 12.

Transcription-coupled changes to chromatin underpin gene silencing by transcriptional interference. Ard R, Allshire RC. Nucleic Acids Res. 2016 Dec 15;44(22):10619-10630. Epub 2016 Sep 8.

Endogenous Mouse Dicer Is an Exclusively Cytoplasmic Protein. Much C, Auchynnikava T, Pavlinic D, Buness A, Rappsilber J, Benes V, Allshire R, O'Carroll D., PLoS Genet. 2016 Jun 2

Centromere localization and function of Mis18 requires Yippee-like domain-mediated oligomerization., Subramanian L, Medina-Pritchard B, Barton R, Spiller F, Kulasegaran-Shylini R, Radaviciute G, Allshire RC, Arockia Jeyaprakash A., EMBO Rep. 2016 Apr;17(4):496-507.

Abo1, a conserved bromodomain AAA-ATPase, maintains global nucleosome occupancy and organisation., Gal C, Murton HE, Subramanian L, Whale AJ, Moore KM, Paszkiewicz K, Codlin S, Bähler J, Creamer KM, Partridge JF, Allshire RC, Kent NA, Whitehall SK., EMBO Rep. 2016 Jan;17(1):79-93.

Epigenetic Regulation of Chromatin States in Schizosaccharomyces pombe., Allshire RC, Ekwall K., Cold Spring Harb Perspect Biol. 2015 Jul 1;7(7):a018770.

Epigenetics. Restricted epigenetic inheritance of H3K9 methylation. Audergon PN, Catania S, Kagansky A, Tong P, Shukla M, Pidoux AL, Allshire RC. Science. 2015 Apr 3;348(6230):132-5.

A nucleosome turnover map reveals that the stability of histone H4 Lys20 methylation depends on histone recycling in transcribed chromatin. Svensson JP, Shukla M, Menendez-Benito V, Norman-Axelsson U, Audergon P, Sinha I, Tanny JC, Allshire RC, Ekwall K. Genome Res. 2015 Mar 16. pii: gr.188870.114. [Epub ahead of print]

Sequence Features and Transcriptional Stalling within Centromere DNA Promote Establishment of CENP-A Chromatin. Catania S, Pidoux AL, Allshire RC. PLoS Genet. 2015 Mar 4;11(3):e1004986.

Pan-Species Small Molecule Disruptors of Heterochromatin-Mediated Transcriptional
Gene Silencing. Castonguay E, White SA, Kagansky A, St-Cyr DJ, Castillo AG, Brugger C, White R, Bonilla C, Spitzer M, Earnshaw WC, Schalch T, Ekwall K, Tyers M, Allshire RC.
Mol Cell Biol. 2014 Dec 8.

Long non-coding RNA-mediated transcriptional interference of a permease gene confers drug tolerance in fission yeast. Ard R, Tong P, Allshire RC.Nat Commun. 2014 Nov 27;5:5576.

A systematic genetic screen identifies new factors influencing centromeric heterochromatin integrity in fission yeast. Bayne EH, Bijos DA, White SA, de Lima Alves F, Rappsilber J, Allshire RC.Genome Biol. 2014 Oct 2;15(10):481.

The RFTS domain of Raf2 is required for Cul4 interaction and heterochromatin
integrity in fission yeast. White SA, Buscaino A, Sanchez-Pulido L, Ponting CP, Nowicki MW, Allshire RC.PLoS One. 2014 Aug 4;9(8):e104161.

A histone H3K36 chromatin switch coordinates DNA double-strand break repair pathway
choice. Pai CC, Deegan RS, Subramanian L, Gal C, Sarkar S, Blaikley EJ, Walker C,
Hulme L, Bernhard E, Codlin S, Bähler J, Allshire R, Whitehall S, Humphrey TC. Nat Commun. 2014 Jun 9;5:4091.

Eic1 links Mis18 with the CCAN/Mis6/Ctf19 complex to promote CENP-A assembly. Subramanian L, Toda NR, Rappsilber J, Allshire RC. Open Biol. 2014 Apr
30;4:140043.

Anarchic centromeres: deciphering order from apparent chaos. Catania S, Allshire RC. Curr Opin Cell Biol. 2014 Feb;26:41-50.

CENP-A confers a reduction in height on octameric nucleosomes. Miell MD, Fuller CJ, Guse A, Barysz HM, Downes A, Owen-Hughes T, Rappsilber J, Straight AF, Allshire RC. Nat Struct Mol Biol. 2013 Jun;20(6):763-5

Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variant. Earnshaw WC, Allshire RC, Black BE, Bloom K, Brinkley BR, Brown W, Cheeseman IM, Choo KH, Copenhaver GP, Deluca JG, Desai A, Diekmann S, Erhardt S, Fitzgerald-Hayes M, Foltz D, Fukagawa T, Gassmann R, Gerlich DW, Glover DM, Gorbsky GJ, Harrison SC, Heun P, Hirota T, Jansen LE, Karpen G, Kops GJ, Lampson MA, Lens SM, Losada A, Luger K, Maiato H, Maddox PS, Margolis RL, Masumoto H, McAinsh AD, Mellone BG, Meraldi P, Musacchio A, Oegema K, O'Neill RJ, Salmon ED, Scott KC, Straight AF, Stukenberg PT, Sullivan BA, Sullivan KF, Sunkel CE, Swedlow JR, Walczak CE, Warburton PE, Westermann S, Willard HF, Wordeman L, Yanagida M, Yen TJ, Yoda K, Cleveland DW. Chromosome Res. 2013 Apr;21(2):101-6.

Telomeric repeats facilitate CENP-A(Cnp1) incorporation via telomere binding proteins. Castillo AG, Pidoux AL, Catania S, Durand-Dubief M, Choi ES, Hamilton G,Ekwall K, Allshire RC. PLoS One. 2013 Jul 31;8(7):e69673.

Distinct roles for Sir2 and RNAi in centromeric heterochromatin nucleation, spreading and maintenance. Buscaino A, Lejeune E, Audergon P, Hamilton G, Pidoux A, Allshire RC. EMBO J. 2013 May 2;32(9):1250-64. doi: 10.1038/emboj.2013.72.

Factors that promote H3 chromatin integrity during transcription prevent promiscuous deposition of CENP-A(Cnp1) in fission yeast.Choi ES, Strålfors A, Catania S, Castillo AG, Svensson JP, Pidoux AL, Ekwall K, Allshire RC. PLoS Genet. 2012 Sep;8(9):e1002985

Quantitative single-molecule microscopy reveals that CENP-A(Cnp1) deposition occurs during G2 in fission yeast. Lando D, Endesfelder U, Berger H, Subramanian L, Dunne PD, McColl J, Klenerman D, Carr AM, Sauer M, Allshire RC, Heilemann M, Laue ED. Open Biol. 2012 Jul;2(7):120078

Raf1 Is a DCAF for the Rik1 DDB1-like protein and has separable roles in siRNA generation and chromatin modification. Buscaino A, White SA, Houston DR, Lejeune E, Simmer F, de Lima Alves F, Diyora PT, Urano T, Bayne EH, Rappsilber J, Allshire RC. PLoS Genet. 2012 Feb;8(2):e1002499.

Identification of noncoding transcripts from within CENP-A chromatin at fission yeast centromeres. Choi ES, Strålfors A, Castillo AG, Durand-Dubief M, Ekwall K, Allshire RC.Identification of noncoding transcripts from within CENP-A chromatin at fission yeast centromeres. J Biol Chem. 2011 Jul 1;286(26):23600-7.

Comparative functional genomics of the fission yeasts. Rhind N, Chen Z, Yassour M, Thompson DA, Haas BJ, Habib N, Wapinski I, Roy S, Lin MF, Heiman DI, Young SK, Furuya K, Guo Y, Pidoux A, Chen HM, Robbertse B, Goldberg JM, Aoki K, Bayne EH, Berlin AM, Desjardins CA, Dobbs E, Dukaj L, Fan L,FitzGerald MG, French C, Gujja S, Hansen K, Keifenheim D, Levin JZ, Mosher RA, Müller CA, Pfiffner J, Priest M, Russ C, Smialowska A, Swoboda P, Sykes SM, Vaughn M, Vengrova S, Yoder R, Zeng Q, Allshire R, Baulcombe D, Birren BW, Brown W, Ekwall K, Kellis M, Leatherwood J, Levin H, Margalit H, Martienssen R, Nieduszynski CA, Spatafora JW, Friedman N, Dalgaard JZ, Baumann P, Niki H, Regev A, Nusbaum C. Science. 2011 May 20;332(6032):930-6.

Common ground: small RNA programming and chromatin modifications. Lejeune E, Allshire RC. Curr Opin Cell Biol. 2011 Jun;23(3):258-65.

On the connection between RNAi and heterochromatin at centromeres. Lejeune E, Bayne EH, Allshire RC. Cold Spring Harb Symp Quant Biol. 2010;75:275-83.

Silencing mediated by the Schizosaccharomyces pombe HIRA complex is dependent upon the Hpc2-like protein, Hip4. Anderson HE, Kagansky A, Wardle J, Rappsilber J, Allshire RC, Whitehall SK. PLoS One. 2010 Oct 18;5(10):e13488.

Stc1: a critical link between RNAi and chromatin modification required for heterochromatin integrity. Bayne EH, White SA, Kagansky A, Bijos DA, Sanchez-Pulido L, Hoe KL, Kim DU, Park HO, Ponting CP, Rappsilber J, Allshire RC. Cell. 2010 Mar 5;140(5):666-77.

Hairpin RNA induces secondary small interfering RNA synthesis and silencing in trans in fission yeast. Simmer F, Buscaino A, Kos-Braun IC, Kagansky A, Boukaba A, Urano T, Kerr AR, Allshire RC. EMBO Rep. 2010 Feb;11(2):112-8

Analysis of small RNA in fission yeast; centromeric siRNAs are potentially generated through a structured RNA. Djupedal I, Kos-Braun IC, Mosher RA, Söderholm N, Simmer F, Hardcastle TJ,Fender A, Heidrich N, Kagansky A, Bayne E, Wagner EG, Baulcombe DC, Allshire RC, Ekwall K. EMBO J. 2009 Dec16;28(24):3832-44

Common ancestry of the CENP-A chaperones Scm3 and HJURP. Sanchez-Pulido L, Pidoux AL, Ponting CP, Allshire RC. Cell. 2009 Jun 26;137(7):1173-4

Synthetic heterochromatin bypasses RNAi and centromeric repeats to establish functional centromeres. Kagansky A, Folco HD, Almeida R, Pidoux AL, Boukaba A, Simmer F, Urano T, Hamilton GL, Allshire RC Science. 2009 Jun 26;324(5935):1716-9.

Fission yeast Scm3: A CENP-A receptor required for integrity of subkinetochore chromatin. Pidoux AL, Choi ES, Abbott JK, Liu X, Kagansky A, Castillo AG, Hamilton GL, Richardson W, Rappsilber J, He X, Allshire RC. Mol Cell. 2009 Feb 13;33(3):299-311.

Splicing factors facilitate RNAi-directed silencing in fission yeast. Bayne EH, Portoso M, Kagansky A, Kos-Braun IC, Urano T, Ekwall K, Alves F, Rappsilber J, Allshire RC. Science. 2008 Oct 24;322(5901):602-6.

A DNA polymerase alpha accessory protein, Mcl1, is required for propagation of centromere structures in fission yeast. Natsume T, Tsutsui Y, Sutani T, Dunleavy EM, Pidoux AL, Iwasaki H, Shirahige K, Allshire RC, Yamao F. PLoS One. 2008 May 21;3(5):e2221

RNAi-mediated chromatin silencing in fission yeast. White SA, Allshire RC. Curr Top Microbiol Immunol. 2008;320:157-83. Review. PubMed PMID: 18268844.

Heterochromatin and RNAi are required to establish CENP-A chromatin at centromeres. Folco HD, Pidoux AL, Urano T, Allshire RC. Science. 2008 Jan 4;319(5859):94-7.

A NASP (N1/N2)-related protein, Sim3, binds CENP-A and is required for its deposition at fission yeast centromeres. Dunleavy EM, Pidoux AL, Monet M, Bonilla C, Richardson W, Hamilton GL, Ekwall K, McLaughlin PJ, Allshire RC. Mol Cell. 2007 Dec 28;28(6):1029-44.

The JmjC domain protein Epe1 prevents unregulated assembly and disassembly of heterochromatin. Trewick SC, Minc E, Antonelli R, Urano T, Allshire RC. EMBO J. 2007 Nov 14;26(22):4670-82. Epub 2007 Oct 18. Erratum in: EMBO J. 2008 Mar 19;27(6):921.

Plasticity of fission yeast CENP-A chromatin driven by relative levels of histone H3 and H4. Castillo AG, Mellone BG, Partridge JF, Richardson W, Hamilton GL, Allshire RC, Pidoux AL. PLoS Genet. 2007 Jul;3(7):e121.

The kinetochore proteins Pcs1 and Mde4 and heterochromatin are required to prevent merotelic orientation. Gregan J, Riedel CG, Pidoux AL, Katou Y, Rumpf C, Schleiffer A, Kearsey SE,Shirahige K, Allshire RC, Nasmyth K. Curr Biol. 2007 Jul 17;17(14):1190-200.

The chromatin-remodeling factor FACT contributes to centromeric heterochromatin independently of RNAi. Lejeune E, Bortfeld M, White SA, Pidoux AL, Ekwall K, Allshire RC, Ladurner AG. Curr Biol. 2007 Jul 17;17(14):1219-24.

DegrAAAded into silence. Bayne EH, White SA, Allshire RC. Cell. 2007 May 18;129(4):651-3. Review. PubMed PMID: 17512398.

Genome-wide studies of histone demethylation catalysed by the fission yeast homologues of mammalian LSD1. Opel M, Lando D, Bonilla C, Trewick SC, Boukaba A, Walfridsson J, Cauwood J, Werler PJ, Carr AM, Kouzarides T, Murzina NV, Allshire RC, Ekwall K, Laue ED.PLoS One. 2007 Apr 18;2(4):e386.

Molecular biology: silencing unlimited. Almeida R, Buscaino A, Allshire RC. Curr Biol. 2006 Aug 22;16(16):R635-8. Review.

Fta2, an essential fission yeast kinetochore component, interacts closely with the conserved Mal2 protein. Kerres A, Jakopec V, Beuter C, Karig I, Pšhlmann J, Pidoux A, Allshire R, Fleig U. Mol Biol Cell. 2006 Oct;17(10):4167-78.

RNA Pol II subunit Rpb7 promotes centromeric transcription and RNAi-directed chromatin silencing. Djupedal I, Portoso M, SpŒhr H, Bonilla C, Gustafsson CM, Allshire RC, Ekwall K. Genes Dev. 2005 Oct 1;19(19):2301-6.

RNA interference, heterochromatin, and centromere function. Allshire RC. Cold Spring Harb Symp Quant Biol. 2004;69:389-95.

RNA-interference-directed chromatin modification coupled to RNA polymerase II transcription. Schramke V, Sheedy DM, Denli AM, Bonila C, Ekwall K, Hannon GJ, Allshire RC. Nature. 2005 Jun 30;435(7046):1275-9. Epub 2005 Jun 19. Retraction in: Schramke V, Sheedy DM, Denli AM, Bonila C, Ekwall K, Hannon GJ, Allshire RC. Nature. 2005 Oct 13;437(7061):1057.

The role of heterochromatin in centromere function. Pidoux AL, Allshire RC.Philos Trans R Soc Lond B Biol Sci. 2005 Mar 29;360(1455):569-79.

RNA silencing and genome regulation. Almeida R, Allshire RC. Trends Cell Biol. 2005 May;15(5):251-8. Review.

Methylation: lost in hydroxylation? Trewick SC, McLaughlin PJ, Allshire RC. EMBO Rep. 2005 Apr;6(4):315-20.

Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Sanders SL, Portoso M, Mata J, BŠhler J, Allshire RC, Kouzarides T. Cell. 2004 Nov 24;119(5):603-14.

Kinetochore and heterochromatin domains of the fission yeast centromere. Pidoux AL, Allshire RC. Chromosome Res. 2004;12(6):521-34.

Those interfering little RNAs! Silencing and eliminating chromatin. Schramke V, Allshire R. Curr Opin Genet Dev. 2004 Apr;14(2):174-80.

Analysis of chromatin in fission yeast. Pidoux A, Mellone B, Allshire R. Methods. 2004 Jul;33(3):252-9.

The Schizosaccharomyces pombe HIRA-like protein Hip1 is required for the periodic expression of histone genes and contributes to the function of complex centromeres. Blackwell C, Martin KA, Greenall A, Pidoux A, Allshire RC, Whitehall SK. Mol Cell Biol. 2004 May;24(10):4309-20.

Cell division: guardian spirit blesses meiosis. Allshire R. Nature. 2004 Feb 5;427(6974):495-7.

Hsk1-Dfp1 is required for heterochromatin-mediated cohesion at centromeres. Bailis JM, Bernard P, Antonelli R, Allshire RC, Forsburg SL. Nat Cell Biol. 2003 Dec;5(12):1111-6. Epub 2003 Nov 16.

Centromere silencing and function in fission yeast is governed by the amino terminus of histone H3. Mellone BG, Ball L, Suka N, Grunstein MR, Partridge JF, Allshire RC. Curr Biol. 2003 Oct 14;13(20):1748-57.

Hairpin RNAs and retrotransposon LTRs effect RNAi and chromatin-based gene silencing. Schramke V, Allshire R Science. 2003 Aug 22;301(5636):1069-74. Retraction in: Allshire R. Science. 2005 Oct 7;310(5745):49.

Chromosome segregation: clamping down on deviant orientations. Pidoux A, Allshire R. Curr Biol. 2003 May 13;13(10):R385-7.

RNA interference is required for normal centromere function in fission yeast. Volpe T, Schramke V, Hamilton GL, White SA, Teng G, Martienssen RA, Allshire RC. Chromosome Res. 2003;11(2):137-46. Erratum in: Chromosome Res. 2003;11(3):584.

Sim4: a novel fission yeast kinetochore protein required for centromeric silencing and chromosome segregation. Pidoux AL, Richardson W, Allshire RC. J Cell Biol. 2003 Apr 28;161(2):295-307.

A new role for the transcriptional corepressor SIN3; regulation of centromeres. Silverstein RA, Richardson W, Levin H, Allshire R, Ekwall K. Curr Biol. 2003 Jan 8;13(1):68-72.

Schizosaccharomyces pombe Git7p, a member of the Saccharomyces cerevisiae Sgtlp family, is required for glucose and cyclic AMP signaling, cell wall integrity, and septation. Schadick K, Fourcade HM, Boumenot P, Seitz JJ, Morrell JL, Chang L, Gould KL, Partridge JF, Allshire RC, Kitagawa K, Hieter P, Hoffman CS. Eukaryot Cell. 2002 Aug;1(4):558-67.

cis-acting DNA from fission yeast centromeres mediates histone H3 methylation and recruitment of silencing factors and cohesin to an ectopic site. Partridge JF, Scott KS, Bannister AJ, Kouzarides T, Allshire RC. Curr Biol. 2002 Oct 1;12(19):1652-60

The mal2p protein is an essential component of the fission yeast centromere. Jin QW, Pidoux AL, Decker C, Allshire RC, Fleig U. Mol Cell Biol. 2002 Oct;22(20):7168-83. PubMed PMID: 12242294; PubMed Central PMCID: PMC139813.

RNAi and heterochromatin--a hushed-up affair. Allshire R. Molecular biology. Science. 2002 Sep 13;297(5588):1818-9.

Fission yeast CENP-B homologs nucleate centromeric heterochromatin by promoting heterochromatin-specific histone tail modifications. Nakagawa H, Lee JK, Hurwitz J, Allshire RC, Nakayama J, Grewal SI, Tanaka K, Murakami Y. Genes Dev. 2002 Jul 15;16(14):1766-78.

Requirement of heterochromatin for cohesion at centromeres. Bernard P, Maure JF, Partridge JF, Genier S, Javerzat JP, Allshire RC. Science. 2001 Dec 21;294(5551):2539-42.

The domain structure of centromeres is conserved from fission yeast to humans. Kniola B, O'Toole E, McIntosh JR, Mellone B, Allshire R, Mengarelli S, Hultenby K, Ekwall K. Mol Biol Cell. 2001 Sep;12(9):2767-75.

A role for DNA polymerase alpha in epigenetic control of transcriptional silencing in fission yeast. Nakayama Ji, Allshire RC, Klar AJ, Grewal SI. EMBO J. 2001 Jun 1;20(11):2857-66.

Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Bannister AJ, Zegerman P, Partridge JF, Miska EA, Thomas JO, Allshire RC, Kouzarides T. Nature. 2001 Mar 1;410(6824):120-4.

Novel functional requirements for non-homologous DNA end joining in Schizosaccharomyces pombe. Manolis KG, Nimmo ER, Hartsuiker E, Carr AM, Jeggo PA, Allshire RC. EMBO J. 2001 Jan 15;20(1-2):210-21.

Live analysis of lagging chromosomes during anaphase and their effect on spindle elongation rate in fission yeast. Pidoux AL, Uzawa S, Perry PE, Cande WZ, Allshire RC. J Cell Sci. 2000 Dec;113 Pt 23:4177-91.

Pausing for thought on the boundaries of imprinting. Allshire R, Bickmore W. Cell. 2000 Sep 15;102(6):705-8.

Centromeres: getting a grip of chromosomes. Pidoux AL, Allshire RC. Curr Opin Cell Biol. 2000 Jun;12(3):308-19.

Dimerisation of a chromo shadow domain and distinctions from the chromodomain as revealed by structural analysis. Cowieson NP, Partridge JF, Allshire RC, McLaughlin PJ. Curr Biol. 2000 May 4;10(9):517-25.

Distinct protein interaction domains and protein spreading in a complex centromere. Partridge JF, Borgstrom B, Allshire RC. Genes Dev. 2000 Apr 1;14(7):783-91.

Fission yeast mutants that alleviate transcriptional silencing in centromeric flanking repeats and disrupt chromosome segregation. Ekwall K, Cranston G, Allshire RC Genetics. 1999 Nov;153(3):1153-69.

The Schizosaccharomyces pombe hst4(+) gene is a SIR2 homologue with silencing and centromeric functions. Freeman-Cook LL, Sherman JM, Brachmann CB, Allshire RC, Boeke JD, Pillus L. Mol Biol Cell. 1999 Oct;10(10):3171-86

Defects in components of the proteasome enhance transcriptional silencing at fission yeast centromeres and impair chromosome segregation. Javerzat JP, McGurk G, Cranston G, Barreau C, Bernard P, Gordon C, Allshire R. Mol Cell Biol. 1999 Jul;19(7):5155-65.

A new member of the Sin3 family of corepressors is essential for cell viability and required for retroelement propagation in fission yeast. Dang VD, Benedik MJ, Ekwall K, Choi J, Allshire RC, Levin HL. Mol Cell Biol. 1999 Mar;19(3):2351-65.

Localization of the 26S proteasome during mitosis and meiosis in fission yeast. Wilkinson CR, Wallace M, Morphew M, Perry P, Allshire R, Javerzat JP, McIntosh JR, Gordon C. EMBO J. 1998 Nov 16;17(22):6465-76.

A Schizosaccharomyces pombe artificial chromosome large DNA cloning system. Young DJ, Nimmo ER, Allshire RC. Nucleic Acids Res. 1998 Nov 15;26(22):5052-60.

The Pad1+ gene encodes a subunit of the 26 S proteasome in fission yeast. Penney M, Wilkinson C, Wallace M, Javerzat JP, Ferrell K, Seeger M, Dubiel W, McKay S, Allshire R, Gordon C. J Biol Chem. 1998 Sep 11;273(37):23938-45.

Genetic characterisation of hda1+, a putative fission yeast histone deacetylase gene. Olsson TG, Ekwall K, Allshire RC, Sunnerhagen P, Partridge JF, Richardson WA. Nucleic Acids Res. 1998 Jul 1;26(13):3247-54

Defective meiosis in telomere-silencing mutants of Schizosaccharomyces pombe. Nimmo ER, Pidoux AL, Perry PE, Allshire RC. Nature. 1998 Apr 23;392(6678):825-8.

Transient inhibition of histone deacetylation alters the structural and functional imprint at fission yeast centromeres. Ekwall K, Olsson T, Turner BM, Cranston G, Allshire RCCell. 1997 Dec 26;91(7):1021-32.

Centromeres, checkpoints and chromatid cohesion. Allshire RC. Curr Opin Genet Dev. 1997 Apr;7(2):264-73. Review. PubMed PMID: 9115433.

Regulation of telomere length and function by a Myb-domain protein in fission yeast. Cooper JP, Nimmo ER, Allshire RC, Cech TR Nature. 1997 Feb20;385(6618):744-7.

Fission yeast genes which disrupt mitotic chromosome segregation when overexpressed. Javerzat JP, Cranston G, Allshire RC. Nucleic Acids Res. 1996 Dec 1;24(23):4676-83.

Mutations in the fission yeast silencing factors clr4+ and rik1+ disrupt the localisation of the chromo domain protein Swi6p and impair centromere function. Ekwall K, Nimmo ER, Javerzat JP, Borgstrom B, Egel R, Cranston G, Allshire R. J Cell Sci. 1996 Nov;109 ( Pt11):2637-48.

The chromodomain protein Swi6: a key component at fission yeast centromeres. Ekwall K, Javerzat JP, Lorentz A, Schmidt H, Cranston G, Allshire R. Science. 1995 Sep 8;26 (5229):1429-31.

Elements of chromosome structure and function in fission yeast. Allshire RC. Semin Cell Biol. 1995 Apr;6(2):55-64.

Mutations derepressing silent centromeric domains in fission yeast disrupt chromosome segregation. Allshire RC, Nimmo ER, Ekwall K, Javerzat JP, Cranston G. Genes Dev. 1995 Jan 15;9(2):218-33.

Telomere-associated chromosome breakage in fission yeast results in variegated expression of adjacent genes. Nimmo ER, Cranston G, Allshire RC. EMBO J. 1994 Aug 15;13(16):3801-11.

Unusual chromosome structure of fission yeast DNA in mouse cells. McManus J, Perry P, Sumner AT, Wright DM, Thomson EJ, Allshire RC, Hastie ND, Bickmore WA. J Cell Sci. 1994 Mar;107 ( Pt 3):469-86.

Position effect variegation at fission yeast centromeres. Allshire RC, Javerzat JP, Redhead NJ, Cranston G. Cell. 1994 Jan 14;76(1):157-69.

Manipulation of large minichromosomes in Schizosaccharomyces pombe with liposome-enhanced transformation. Allshire RC. Methods Enzymol. 1992;216:614-31.

Introduction of large linear minichromosomes into Schizosaccharomyces pombe by an improved transformation procedure. Allshire RC Proc Natl Acad Sci U S A. 1990 Jun;87(11):4043-7.

Telomeric repeat from T. thermophila cross hybridizes with human telomeres. Allshire RC, Gosden JR, Cross SH, Cranston G, Rout D, Sugawara N, Szostak JW, Fantes PA, Hastie ND. Nature. 1988 Apr 14;332(6165):656-9.

A fission yeast chromosome can replicate autonomously in mouse cells. Allshire RC, Cranston G, Gosden JR, Maule JC, Hastie ND, Fantes PA. Cell. 1987 Jul 31;50(3):391-403.