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dc.date.accessioned2018-09-06T12:51:25Z
dc.date.available2018-09-06T12:51:25Z
dc.date.created2017-09-08T21:30:53Z
dc.date.issued2017
dc.identifier.citationFuglerud, Bettina Maria Lemma, Roza Berhanu Wanichawan, Pimthanya Sundaram, Arvind Eskeland, Ragnhild Gabrielsen, Odd Stokke . A c-Myb mutant causes deregulated differentiation due to impaired histone binding and abrogated pioneer factor function. Nucleic Acids Research. 2017, 45(13), 7681-7696
dc.identifier.urihttp://hdl.handle.net/10852/64171
dc.description.abstractThe transcription factor c-Myb is involved in early differentiation and proliferation of haematopoietic cells, where it operates as a regulator of self-renewal and multi-lineage differentiation. Deregulated c-Myb plays critical roles in leukaemias and other human cancers. Due to its role as a master regulator, we hypothesized it might function as a pioneer transcription factor. Our approach to test this was to analyse a mutant of c-Myb, D152V, previously reported to cause haematopoietic defects in mice by an unknown mechanism. Our transcriptome data from K562 cells indicates that this mutation specifically affects c-Myb's ability to regulate genes involved in differentiation, causing failure in c-Myb's ability to block differentiation. Furthermore, we see a major effect of this mutation in assays where chromatin opening is involved. We show that each repeat in the minimal DNA-binding domain of c-Myb binds to histones and that D152V disrupts histone binding of the third repeat. ATAC-seq data indicates this mutation impairs the ability of c-Myb to cause chromatin opening at specific sites. Taken together, our findings support that c-Myb acts as a pioneer factor and show that D152V impairs this function. The D152V mutant is the first mutant of a transcription factor specifically destroying pioneer factor function.en_US
dc.languageEN
dc.publisherOxford University Press
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.titleA c-Myb mutant causes deregulated differentiation due to impaired histone binding and abrogated pioneer factor functionen_US
dc.typeJournal articleen_US
dc.creator.authorFuglerud, Bettina Maria
dc.creator.authorLemma, Roza Berhanu
dc.creator.authorWanichawan, Pimthanya
dc.creator.authorSundaram, Arvind
dc.creator.authorEskeland, Ragnhild
dc.creator.authorGabrielsen, Odd Stokke
cristin.unitcode185,15,29,40
cristin.unitnameSeksjon for biokjemi og molekylærbiologi
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2
dc.identifier.cristin1492317
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nucleic Acids Research&rft.volume=45&rft.spage=7681&rft.date=2017
dc.identifier.jtitleNucleic Acids Research
dc.identifier.volume45
dc.identifier.issue13
dc.identifier.startpage7681
dc.identifier.endpage7696
dc.identifier.doihttp://dx.doi.org/10.1093/nar/gkx364
dc.identifier.urnURN:NBN:no-66703
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn0305-1048
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/64171/1/Nucleic%2BAcids%2BRes.%2B2017%2BFuglerud.pdf
dc.type.versionPublishedVersion
dc.relation.projectKF/419436
dc.relation.projectNFR/240768
dc.relation.projectNOTUR/NORSTORE/NN9374K


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