Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivo

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  • dc.contributor.author Otterstrom, Jason
  • dc.contributor.author Castells García, Àlvaro, 1991-
  • dc.contributor.author Vicario, Chiara
  • dc.contributor.author Gómez García, Pablo
  • dc.contributor.author Cosma, Maria Pia, 1970-
  • dc.contributor.author Lakadamyali, Melike
  • dc.date.accessioned 2020-04-06T10:06:34Z
  • dc.date.available 2020-04-06T10:06:34Z
  • dc.date.issued 2019
  • dc.description.abstract Chromatin organization is crucial for regulating gene expression. Previously, we showed that nucleosomes form groups, termed clutches. Clutch size correlated with the pluripotency grade of mouse embryonic stem cells and human induced pluripotent stem cells. Recently, it was also shown that regions of the chromatin containing activating epigenetic marks were composed of small and dispersed chromatin nanodomains with lower DNA density compared to the larger silenced domains. Overall, these results suggest that clutch size may regulate DNA packing density and gene activity. To directly test this model, we carried out 3D, two-color super-resolution microscopy of histones and DNA with and without increased histone tail acetylation. Our results showed that lower percentage of DNA was associated with nucleosome clutches in hyperacetylated cells. We further showed that the radius and compaction level of clutch-associated DNA decreased in hyperacetylated cells, especially in regions containing several neighboring clutches. Importantly, this change was independent of clutch size but dependent on the acetylation state of the clutch. Our results directly link the epigenetic state of nucleosome clutches to their DNA packing density. Our results further provide in vivo support to previous in vitro models that showed a disruption of nucleosome-DNA interactions upon hyperacetylation.
  • dc.description.sponsorship European Union's Horizon 2020 Research and Innovation Programme [CellViewer No. 686637 to M.L. and M.P.C.], Marie Sklodowska-Curie Individual Fellowship [VCSD G.A. 656873 to J.J.O], Marie Sklodowska-Curie COFUND action [ICFONest+ GA 609416 to J.J.O]; Ministerio de Economia y Competitividad y Fondo Europeo de Desarrollo Regional (FEDER) [SAF2011-28580, BFU2015-71984 to M.P.C.]; AGAUR grant from Secretaria d′Universitats i Investigació del Departament d′Economia i Coneixement de la Generalitat de Catalunya [2014SGR1137 to M.P.C.]; ‘La Caixa-Severo Ochoa’ pre-doctoral fellowship (to A.C.G.); Spanish Ministry of Economy and Competitiveness (MEIC); EMBL partnership, Centro de Excelencia Severo Ochoa; CERCA Programme/Generalitat de Catalunya (to M.P.C.). Funding for open access charge: European Union’s Horizon 2020 Research and Innovation Programme [CellViewer No. 686637 to M.L. and M.P.C.].
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Otterstrom J, Castells-Garcia A, Vicario C, Gomez-Garcia PA, Cosma MP, Lakadamyali M. Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivo. Nucleic Acids Res. 2019; 47(16):8470-84. DOI: 10.1093/nar/gkz593
  • dc.identifier.doi http://dx.doi.org/10.1093/nar/gkz593
  • dc.identifier.issn 0305-1048
  • dc.identifier.uri http://hdl.handle.net/10230/44160
  • dc.language.iso eng
  • dc.publisher Oxford University Press
  • dc.relation.ispartof Nucleic Acids Res. 2019; 47(16):8470-84
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/686637
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/656873
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/609416
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-28580
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-71984
  • dc.rights © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Chromatin and epigenetics
  • dc.subject.keyword Gene regulation
  • dc.title Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivo
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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