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dc.contributor.authorSouthall, SMen_US
dc.contributor.authorCronin, NBen_US
dc.contributor.authorWilson, JRen_US
dc.date.accessioned2018-08-03T13:26:59Z
dc.date.issued2014-01en_US
dc.identifier1en_US
dc.identifier.citationNUCLEIC ACIDS RESEARCH, 2014, 42 pp. 661 - 671en_US
dc.identifier.issn0305-1048en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2261
dc.identifier.eissn1362-4962en_US
dc.identifier.doi10.1093/nar/gkt776en_US
dc.description.abstractThe delivery of site-specific post-translational modifications to histones generates an epigenetic regulatory network that directs fundamental DNA-mediated processes and governs key stages in development. Methylation of histone H4 lysine-20 has been implicated in DNA repair, transcriptional silencing, genomic stability and regulation of replication. We present the structure of the histone H4K20 methyltransferase Suv4-20h2 in complex with its histone H4 peptide substrate and S-adenosyl methionine cofactor. Analysis of the structure reveals that the Suv4-20h2 active site diverges from the canonical SET domain configuration and generates a high degree of both substrate and product specificity. Together with supporting biochemical data comparing Suv4-20h1 and Suv4-20h2, we demonstrate that the Suv4-20 family enzymes take a previously mono-methylated H4K20 substrate and generate an exclusively di-methylated product. We therefore predict that other enzymes are responsible for the tri-methylation of histone H4K20 that marks silenced heterochromatin.en_US
dc.format.extent661 - 671en_US
dc.languageEnglishen_US
dc.language.isoEnglishen_US
dc.publisherOXFORD UNIV PRESSen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleA novel route to product specificity in the Suv4-20 family of histone H4K20 methyltransferasesen_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1093/nar/gkt776en_US
rioxxterms.licenseref.startdate2014-01en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfNUCLEIC ACIDS RESEARCHen_US
pubs.notesaffiliation: Wilson, JR (Reprint Author), Natl Inst Med Res, Div Mol Struct, Mill Hill, London NW7 1AA, England. Southall, Stacey M.; Cronin, Nora B.; Wilson, Jon R., Inst Canc Res, Chester Beatty Labs, Div Struct Biol, London SW3 6JB, England. keywords-plus: H4 LYSINE 20; DOMAIN PROTEIN METHYLTRANSFERASES; FUNCTIONAL-CHARACTERIZATION; STRUCTURAL BASIS; DNA-DAMAGE; METHYLATION; CHROMATIN; PR-SET7; RECRUITMENT; TRIMETHYLATION research-areas: Biochemistry & Molecular Biology web-of-science-categories: Biochemistry & Molecular Biology author-email: [email protected] funding-acknowledgement: Institute of Cancer Research; NHS; Medical Research Council [U117584222] funding-text: The Institute of Cancer Research and benefits from infra-structural support for structural biology by Cancer Research UK. We acknowledge NHS funding to the NIHR Biomedical Research Centre. Funding for open access charge: the Medical Research Council [Unit Programme number U117584222]. number-of-cited-references: 49 times-cited: 14 usage-count-last-180-days: 0 usage-count-since-2013: 10 journal-iso: Nucleic Acids Res. doc-delivery-number: AA5KF unique-id: ISI:000331136000058 oa: gold da: 2018-08-03en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Chromatin Regulation
pubs.volume42en_US
pubs.embargo.termsNot knownen_US
icr.researchteamChromatin Regulationen_US
dc.contributor.icrauthorWilson, Jonathan Roberten_US
dc.contributor.icrauthorCronin, Noraen_US
dc.contributor.icrauthorSouthall, Staceyen_US


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