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dc.contributor.authorWinick-Ng, Warren
dc.contributor.authorKukalev, Alexander
dc.contributor.authorHarabula, Izabela
dc.contributor.authorZea-Redondo, Luna
dc.contributor.authorSzabó, Dominik
dc.contributor.authorMeijer, Mandy
dc.contributor.authorSerebreni, Leonid
dc.contributor.authorZhang, Yingnan
dc.contributor.authorBianco, Simona
dc.contributor.authorChiariello, Andrea M
dc.contributor.authorIrastorza-Azcarate, Ibai
dc.contributor.authorThieme, Christoph J
dc.contributor.authorSparks, Thomas M
dc.contributor.authorCarvalho, Sílvia
dc.contributor.authorFiorillo, Luca
dc.contributor.authorMusella, Francesco
dc.contributor.authorIrani, Ehsan
dc.contributor.authorTorlai Triglia, Elena
dc.contributor.authorKolodziejczyk, Aleksandra A
dc.contributor.authorAbentung, Andreas
dc.contributor.authorApostolova, Galina
dc.contributor.authorPaul, Eleanor J
dc.contributor.authorFranke, Vedran
dc.contributor.authorKempfer, Rieke
dc.contributor.authorAkalin, Altuna
dc.contributor.authorTeichmann, Sarah
dc.contributor.authorDechant, Georg
dc.contributor.authorUngless, Mark A
dc.contributor.authorNicodemi, Mario
dc.contributor.authorWelch, Lonnie
dc.contributor.authorCastelo-Branco, Gonçalo
dc.contributor.authorPombo, Ana
dc.date.accessioned2022-01-07T16:52:20Z
dc.date.available2022-01-07T16:52:20Z
dc.date.issued2021-11
dc.identifier.issn0028-0836
dc.identifier.otherPMC8612935
dc.identifier.other34789882
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332411
dc.description.abstractThe three-dimensional (3D) structure of chromatin is intrinsically associated with gene regulation and cell function1-3. Methods based on chromatin conformation capture have mapped chromatin structures in neuronal systems such as in vitro differentiated neurons, neurons isolated through fluorescence-activated cell sorting from cortical tissues pooled from different animals and from dissociated whole hippocampi4-6. However, changes in chromatin organization captured by imaging, such as the relocation of Bdnf away from the nuclear periphery after activation7, are invisible with such approaches8. Here we developed immunoGAM, an extension of genome architecture mapping (GAM)2,9, to map 3D chromatin topology genome-wide in specific brain cell types, without tissue disruption, from single animals. GAM is a ligation-free technology that maps genome topology by sequencing the DNA content from thin (about 220 nm) nuclear cryosections. Chromatin interactions are identified from the increased probability of co-segregation of contacting loci across a collection of nuclear slices. ImmunoGAM expands the scope of GAM to enable the selection of specific cell types using low cell numbers (approximately 1,000 cells) within a complex tissue and avoids tissue dissociation2,10. We report cell-type specialized 3D chromatin structures at multiple genomic scales that relate to patterns of gene expression. We discover extensive 'melting' of long genes when they are highly expressed and/or have high chromatin accessibility. The contacts most specific of neuron subtypes contain genes associated with specialized processes, such as addiction and synaptic plasticity, which harbour putative binding sites for neuronal transcription factors within accessible chromatin regions. Moreover, sensory receptor genes are preferentially found in heterochromatic compartments in brain cells, which establish strong contacts across tens of megabases. Our results demonstrate that highly specific chromatin conformations in brain cells are tightly related to gene regulation mechanisms and specialized functions.
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 1476-4687
dc.sourcenlmid: 0410462
dc.titleCell-type specialization is encoded by specific chromatin topologies.
dc.typeArticle
dc.date.updated2022-01-07T16:52:20Z
prism.endingPage691
prism.issueIdentifier7886
prism.publicationNameNature
prism.startingPage684
prism.volume599
dc.identifier.doi10.17863/CAM.79857
dcterms.dateAccepted2021-09-30
rioxxterms.versionofrecord10.1038/s41586-021-04081-2
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidWinick-Ng, Warren [0000-0002-8716-5558]
dc.contributor.orcidMeijer, Mandy [0000-0003-3314-1224]
dc.contributor.orcidBianco, Simona [0000-0001-5819-060X]
dc.contributor.orcidChiariello, Andrea M [0000-0002-6112-0167]
dc.contributor.orcidThieme, Christoph J [0000-0002-1566-0971]
dc.contributor.orcidFiorillo, Luca [0000-0003-2967-0123]
dc.contributor.orcidTorlai Triglia, Elena [0000-0002-6059-0116]
dc.contributor.orcidPaul, Eleanor J [0000-0003-1183-9285]
dc.contributor.orcidFranke, Vedran [0000-0003-3606-6792]
dc.contributor.orcidAkalin, Altuna [0000-0002-0468-0117]
dc.contributor.orcidTeichmann, Sarah [0000-0002-6294-6366]
dc.contributor.orcidCastelo-Branco, Gonçalo [0000-0003-2247-9393]
dc.contributor.orcidPombo, Ana [0000-0002-7493-6288]
dc.identifier.eissn1476-4687
pubs.funder-project-idNIDDK NIH HHS (U54 DK107977)
pubs.funder-project-idEuropean Research Council (681893)
pubs.funder-project-idNHGRI NIH HHS (UM1 HG011585)
cam.issuedOnline2021-11-17


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