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dc.contributor.authorEl-Sharnouby, Sen
dc.contributor.authorFischer, Bettinaen
dc.contributor.authorMagbanua, JPen
dc.contributor.authorUmans, Ben
dc.contributor.authorFlower, Ren
dc.contributor.authorChoo, SWen
dc.contributor.authorRussell, Steveen
dc.contributor.authorWhite, Roberten
dc.date.accessioned2017-05-11T16:53:33Z
dc.date.available2017-05-11T16:53:33Z
dc.date.issued2017-03-10en
dc.identifier.issn1932-6203
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/264199
dc.description.abstractIt is now well established that eukaryote genomes have a common architectural organization into topologically associated domains (TADs) and evidence is accumulating that this organization plays an important role in gene regulation. However, the mechanisms that partition the genome into TADs and the nature of domain boundaries are still poorly understood. We have investigated boundary regions in the Drosophila genome and find that they can be identified as domains of very low H3K27me3. The genome-wide H3K27me3 profile partitions into two states; very low H3K27me3 identifies Depleted (D) domains that contain housekeeping genes and their regulators such as the histone acetyltransferase-containing NSL complex, whereas domains containing moderate-to-high levels of H3K27me3 (Enriched or E domains) are associated with regulated genes, irrespective of whether they are active or inactive. The D domains correlate with the boundaries of TADs and are enriched in a subset of architectural proteins, particularly Chromator, BEAF-32, and Z4/Putzig. However, rather than being clustered at the borders of these domains, these proteins bind throughout the H3K27me3-depleted regions and are much more strongly associated with the transcription start sites of housekeeping genes than with the H3K27me3 domain boundaries. While we have not demonstrated causality, we suggest that the D domain chromatin state, characterised by very low or absent H3K27me3 and established by housekeeping gene regulators, acts to separate topological domains thereby setting up the domain architecture of the genome.
dc.description.sponsorshipThis work was supported by the Wellcome Trust (https://wellcome.ac.uk/, grant 089834/Z/09/Z to RW, SR), by the University of Malaya High Impact Research (hir.um.edu.my, grant UM.C/625/HIR/MOHE/CHAN-08 to SWC) from the Ministry of Higher Education Malaysia, and by the BBSRC (www.bbsrc.ac.uk, grant BB/M007081/1 to RW, SR). BU was funded by a Cambridge Marshall Scholarship.
dc.languageengen
dc.language.isoenen
dc.publisherPLOS
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleRegions of very low H3K27me3 partition the Drosophila genome into topological domainsen
dc.typeArticle
prism.issueIdentifier3en
prism.numbere0172725en
prism.publicationDate2017en
prism.publicationNamePLOS Oneen
prism.volume12en
dc.identifier.doi10.17863/CAM.9558
dcterms.dateAccepted2017-02-08en
rioxxterms.versionofrecord10.1371/journal.pone.0172725en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-03-10en
dc.contributor.orcidFischer, Bettina [0000-0003-2821-6287]
dc.contributor.orcidRussell, Steve [0000-0003-0546-3031]
dc.contributor.orcidWhite, Robert [0000-0002-0019-8227]
dc.identifier.eissn1932-6203
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/M007081/1)
pubs.funder-project-idWellcome Trust (089834/Z/09/Z)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International