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dc.contributor.authorJiao, F
dc.contributor.authorLi, Z
dc.contributor.authorHe, C
dc.contributor.authorXu, W
dc.contributor.authorYang, G
dc.contributor.authorLiu, T
dc.contributor.authorShen, H
dc.contributor.authorCai, J
dc.contributor.authorAnastas, JN
dc.contributor.authorMao, Y
dc.contributor.authorYu, Y
dc.contributor.authorLan, F
dc.contributor.authorShi, YG
dc.contributor.authorJones, C
dc.contributor.authorXu, Y
dc.contributor.authorBaker, SJ
dc.contributor.authorShi, Y
dc.contributor.authorGuo, R
dc.date.accessioned2020-11-03T16:11:18Z
dc.date.issued2020-07-17
dc.identifier.citationScience advances, 2020, 6 (29), pp. eaba2113 - ?
dc.identifier.issn2375-2548
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4212
dc.identifier.eissn2375-2548
dc.identifier.doi10.1126/sciadv.aba2113
dc.description.abstractHistone H3 point mutations have been identified in incurable pediatric brain cancers, but the mechanisms through which these mutations drive tumorigenesis are incompletely understood. Here, we provide evidence that RACK7 (ZMYND8) recognizes the histone H3.3 patient mutation (H3.3G34R) in vitro and in vivo. We show that RACK7 binding to H3.3G34R suppresses transcription of CIITA , which is the master regulator of MHC (major histocompatibility complex) class II molecules and genes involved in vesicular transport of MHC class II molecules to the cell surface, resulting in suppression of MHC class II molecule expression and transport. CRISPR-based knock-in correction of the H3.3G34R mutation in human pediatric glioblastoma (pGBM) cells significantly reduces overall RACK7 chromatin binding and derepresses the same set of genes as does knocking out RACK7 in the H3.3G34R pGBM cells. By demonstrating that H3.3G34R and RACK7 work together, our findings suggest a potential molecular mechanism by which H3.3G34R promotes cancer.
dc.formatElectronic-eCollection
dc.format.extenteaba2113 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0
dc.titleRACK7 recognizes H3.3G34R mutation to suppress expression of MHC class II complex components and their delivery pathway in pediatric glioblastoma.
dc.typeJournal Article
dcterms.dateAccepted2020-05-28
rioxxterms.versionofrecord10.1126/sciadv.aba2113
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc/4.0
rioxxterms.licenseref.startdate2020-07-17
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfScience advances
pubs.issue29
pubs.notesNot 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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team
pubs.publication-statusPublished
pubs.volume6
pubs.embargo.termsNot known
icr.researchteamGlioma Teamen_US
dc.contributor.icrauthorJones, Chrisen


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Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc/4.0