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Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore

2011-01-19Journal article Open access
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dc.contributor.authorBergmann, Jan H
dc.contributor.authorRodríguez, Mariluz Gómez
dc.contributor.authorMartins, Nuno M C
dc.contributor.authorKimura, Hiroshi
dc.contributor.authorKelly, David A
dc.contributor.authorMasumoto, Hiroshi
dc.contributor.authorLarionov, Vladimir
dc.contributor.authorJansen, Lars E T
dc.contributor.authorEarnshaw, William C
dc.date.accessioned2016-05-24T10:33:46Z
dc.date.available2016-05-24T10:33:46Z
dc.date.issued2011-01-19
dc.description.abstractKinetochores assemble on distinct 'centrochromatin' containing the histone H3 variant CENP-A and interspersed nucleosomes dimethylated on H3K4 (H3K4me2). Little is known about how the chromatin environment at active centromeres governs centromeric structure and function. Here, we report that centrochromatin resembles K4-K36 domains found in the body of some actively transcribed housekeeping genes. By tethering the lysine-specific demethylase 1 (LSD1), we specifically depleted H3K4me2, a modification thought to have a role in transcriptional memory, from the kinetochore of a synthetic human artificial chromosome (HAC). H3K4me2 depletion caused kinetochores to suffer a rapid loss of transcription of the underlying α-satellite DNA and to no longer efficiently recruit HJURP, the CENP-A chaperone. Kinetochores depleted of H3K4me2 remained functional in the short term, but were defective in incorporation of CENP-A, and were gradually inactivated. Our data provide a functional link between the centromeric chromatin, α-satellite transcription, maintenance of CENP-A levels and kinetochore stability.pt_PT
dc.description.sponsorshipWellcome Trust and NMCM PhD studentship; FCT studentships and grant: (BIA‐PRO/100537/2008); Fundação Calouste Gulbenkian; European Commission FP7 programme; EMBO installation grant; NIH (intramural research program); National Cancer Institute; Center for Cancer Research; Ministry of Education, Science, Sports and Culture of Japan; MEXT of Japan.pt_PT
dc.identifier.citationBergmann, J. H., Rodríguez, M. G., Martins, N. M. C., Kimura, H., Kelly, D. A., Masumoto, H., Larionov, V., Jansen, L. E. T., Earnshaw, W. C. (2011). Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore. EMBO J., 30(2), 328–340.pt_PT
dc.identifier.doi10.1038/emboj.2010.329pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/613
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNature Publishing Grouppt_PT
dc.relation.publisherversionhttp://emboj.embopress.org/content/30/2/328.exportpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/pt_PT
dc.subjectAutoantigenspt_PT
dc.subjectCentromerept_PT
dc.subjectChromatinpt_PT
dc.subjectChromatin Immunoprecipitationpt_PT
dc.subjectChromosomal Proteins, Non-Histonept_PT
dc.subjectChromosomes, Artificial, Humanpt_PT
dc.subjectDNA Primerspt_PT
dc.subjectDNA-Binding Proteinspt_PT
dc.subjectEpigenesis, Geneticpt_PT
dc.subjectGenetic Engineeringpt_PT
dc.subjectHistonespt_PT
dc.subjectHumanspt_PT
dc.subjectKinetochorespt_PT
dc.subjectNucleosomespt_PT
dc.subjectReverse Transcriptase Polymerase Chain Reactionpt_PT
dc.titleEpigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochorept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage340pt_PT
oaire.citation.issue2pt_PT
oaire.citation.startPage328pt_PT
oaire.citation.titleThe EMBO Journalpt_PT
oaire.citation.volume30pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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