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Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal

2015-01Journal article Open access
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dc.contributor.authorMateo, Juan L
dc.contributor.authorvan den Berg, Debbie L C
dc.contributor.authorHaeussler, Maximilian
dc.contributor.authorDrechsel, Daniela
dc.contributor.authorGaber, Zachary B
dc.contributor.authorCastro, Diogo S
dc.contributor.authorRobson, Paul
dc.contributor.authorCrawford, Gregory E
dc.contributor.authorFlicek, Paul
dc.contributor.authorEttwiller, Laurence
dc.contributor.authorWittbrodt, Joachim
dc.contributor.authorGuillemot, François
dc.contributor.authorMartynoga, Ben
dc.date.accessioned2015-10-20T16:11:02Z
dc.date.available2015-10-21T00:30:09Z
dc.date.issued2015-01
dc.description.abstractThe gene regulatory network (GRN) that supports neural stem cell (NS cell) self-renewal has so far been poorly characterized. Knowledge of the central transcription factors (TFs), the noncoding gene regulatory regions that they bind to, and the genes whose expression they modulate will be crucial in unlocking the full therapeutic potential of these cells. Here, we use DNase-seq in combination with analysis of histone modifications to identify multiple classes of epigenetically and functionally distinct cis-regulatory elements (CREs). Through motif analysis and ChIP-seq, we identify several of the crucial TF regulators of NS cells. At the core of the network are TFs of the basic helix-loop-helix (bHLH), nuclear factor I (NFI), SOX, and FOX families, with CREs often densely bound by several of these different TFs. We use machine learning to highlight several crucial regulatory features of the network that underpin NS cell self-renewal and multipotency. We validate our predictions by functional analysis of the bHLH TF OLIG2. This TF makes an important contribution to NS cell self-renewal by concurrently activating pro-proliferation genes and preventing the untimely activation of genes promoting neuronal differentiation and stem cell quiescence.pt_PT
dc.description.sponsorshipWelcome Trust grants: (WT095908, WT098051), FEBS Long-Term Fellowship, Medical Research Council Grant-in-Aid (U117570528).pt_PT
dc.identifier10.1101/gr.173435.114
dc.identifier.doi10.1101/gr.173435.114
dc.identifier.urihttp://hdl.handle.net/10400.7/415
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherCold Spring Harbor Lab Presspt_PT
dc.relationCis-regulatory logic of the transcriptional control in neural stem cells
dc.relation.publisherversionhttp://genome.cshlp.org/content/25/1/41.longpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectStem Cellspt_PT
dc.subjectOLIG2pt_PT
dc.titleCharacterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewalpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCis-regulatory logic of the transcriptional control in neural stem cells
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/223210/EU
oaire.citation.endPage56pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage41pt_PT
oaire.citation.titleGenome Researchpt_PT
oaire.citation.volume25pt_PT
oaire.fundingStreamFP7
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication028562e4-709a-46d2-a07f-5124bcbc9f53
relation.isProjectOfPublication.latestForDiscovery028562e4-709a-46d2-a07f-5124bcbc9f53

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