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

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 o...

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Autores: Otterstrom, Jason, Castells García, Àlvaro, 1991-, Vicario, Chiara, Gómez García, Pablo, Cosma, Maria Pia, 1970-, Lakadamyali, Melike
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/44160
Acceso en línea:http://hdl.handle.net/10230/44160
http://dx.doi.org/10.1093/nar/gkz593
Access Level:acceso abierto
Palabra clave:Chromatin and epigenetics
Gene regulation
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spelling Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivoOtterstrom, JasonCastells García, Àlvaro, 1991-Vicario, ChiaraGómez García, PabloCosma, Maria Pia, 1970-Lakadamyali, MelikeChromatin and epigeneticsGene regulationChromatin 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.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.].Oxford University Press202020202019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/44160http://dx.doi.org/10.1093/nar/gkz593reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésNucleic Acids Res. 2019; 47(16):8470-84info:eu-repo/grantAgreement/EC/H2020/686637info:eu-repo/grantAgreement/EC/H2020/656873info:eu-repo/grantAgreement/EC/FP7/609416info:eu-repo/grantAgreement/ES/3PN/SAF2011-28580info:eu-repo/grantAgreement/ES/1PE/BFU2015-71984© 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.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/441602026-06-12T07:21:37Z
dc.title.none.fl_str_mv Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivo
title Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivo
spellingShingle Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivo
Otterstrom, Jason
Chromatin and epigenetics
Gene regulation
title_short Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivo
title_full Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivo
title_fullStr Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivo
title_full_unstemmed Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivo
title_sort Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivo
dc.creator.none.fl_str_mv Otterstrom, Jason
Castells García, Àlvaro, 1991-
Vicario, Chiara
Gómez García, Pablo
Cosma, Maria Pia, 1970-
Lakadamyali, Melike
author Otterstrom, Jason
author_facet Otterstrom, Jason
Castells García, Àlvaro, 1991-
Vicario, Chiara
Gómez García, Pablo
Cosma, Maria Pia, 1970-
Lakadamyali, Melike
author_role author
author2 Castells García, Àlvaro, 1991-
Vicario, Chiara
Gómez García, Pablo
Cosma, Maria Pia, 1970-
Lakadamyali, Melike
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Chromatin and epigenetics
Gene regulation
topic Chromatin and epigenetics
Gene regulation
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/44160
http://dx.doi.org/10.1093/nar/gkz593
url http://hdl.handle.net/10230/44160
http://dx.doi.org/10.1093/nar/gkz593
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nucleic Acids Res. 2019; 47(16):8470-84
info:eu-repo/grantAgreement/EC/H2020/686637
info:eu-repo/grantAgreement/EC/H2020/656873
info:eu-repo/grantAgreement/EC/FP7/609416
info:eu-repo/grantAgreement/ES/3PN/SAF2011-28580
info:eu-repo/grantAgreement/ES/1PE/BFU2015-71984
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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