dc.contributor.author | Southall, SM | |
dc.contributor.author | Cronin, NB | |
dc.contributor.author | Wilson, JR | |
dc.date.accessioned | 2018-08-03T13:26:59Z | |
dc.date.issued | 2014-01-01 | |
dc.identifier | 1 | |
dc.identifier.citation | NUCLEIC ACIDS RESEARCH, 2014, 42 pp. 661 - 671 | |
dc.identifier.issn | 0305-1048 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/2261 | |
dc.identifier.eissn | 1362-4962 | |
dc.identifier.doi | 10.1093/nar/gkt776 | |
dc.description.abstract | The 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. | |
dc.format.extent | 661 - 671 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | OXFORD UNIV PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | A novel route to product specificity in the Suv4-20 family of histone H4K20 methyltransferases | |
dc.type | Journal Article | |
rioxxterms.versionofrecord | 10.1093/nar/gkt776 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2014-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | NUCLEIC ACIDS RESEARCH | |
pubs.notes | affiliation: 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: 2018-08-03 | |
pubs.notes | Not known | |
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.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.volume | 42 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Chromatin Regulation | |
dc.contributor.icrauthor | Cronin, Nora | |
dc.contributor.icrauthor | Wilson, Jonathan Robert | |