SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina

Long interspersed elements-1 (LINE-1, L1) are retrotransposons that hold the capacity of self-propagation in the genome with potential mutagenic outcomes. How somatic cells restrict L1 activity and how this process becomes dysfunctional during aging and in cancer cells is poorly understood. L1s are...

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Autores: Vazquez, Berta N., Thackray, Joshua K., Simonet, Nicolás G., Chahar, Sanjay, Kane-Goldsmith, Noriko, Newkirk, Simon J., Lee, Suman, Xing, Jinchuan, Verzi, Michael P., An, Wenfeng, Vaquero García, Alejandro, Tischfield, Jay A., Serrano, Lourdes
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/171238
Acceso en línea:https://hdl.handle.net/2445/171238
Access Level:acceso abierto
Palabra clave:Regulació genètica
Epigenètica
Cromatina
Genetic regulation
Epigenetics
Chromatin
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spelling SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear laminaVazquez, Berta N.Thackray, Joshua K.Simonet, Nicolás G.Chahar, SanjayKane-Goldsmith, NorikoNewkirk, Simon J.Lee, SumanXing, JinchuanVerzi, Michael P.An, WenfengVaquero García, AlejandroTischfield, Jay A.Serrano, LourdesRegulació genèticaEpigenèticaCromatinaGenetic regulationEpigeneticsChromatinLong interspersed elements-1 (LINE-1, L1) are retrotransposons that hold the capacity of self-propagation in the genome with potential mutagenic outcomes. How somatic cells restrict L1 activity and how this process becomes dysfunctional during aging and in cancer cells is poorly understood. L1s are enriched at lamin-associated domains, heterochromatic regions of the nuclear periphery. Whether this association is necessary for their repression has been elusive. Here we show that the sirtuin family member SIRT7 participates in the epigenetic transcriptional repression of L1 genome-wide in both mouse and human cells. SIRT7 depletion leads to increased L1 expression and retrotransposition. Mechanistically, we identify a novel interplay between SIRT7 and Lamin A/C in L1 repression. Our results demonstrate that SIRT7-mediated H3K18 deacetylation regulates L1 expression and promotes L1 association with elements of the nuclear lamina. The failure of such activity might contribute to the observed genome instability and compromised viability in SIRT7 knockout mice. Overall, our results reveal a novel function of SIRT7 on chromatin organization by mediating the anchoring of L1 to the nuclear envelope, and a new functional link of the nuclear lamina with transcriptional repression.Oxford University Press2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/171238Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1093/nar/gkz519Nucleic Acids Research, 2019, vol. 47, num. 15, p. 7870-7885https://doi.org/10.1093/nar/gkz519cc by-nc (c) Vazquez et al., 2019http://creativecommons.org/licenses/by-nc/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1712382026-05-27T06:46:51Z
dc.title.none.fl_str_mv SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina
title SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina
spellingShingle SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina
Vazquez, Berta N.
Regulació genètica
Epigenètica
Cromatina
Genetic regulation
Epigenetics
Chromatin
title_short SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina
title_full SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina
title_fullStr SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina
title_full_unstemmed SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina
title_sort SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina
dc.creator.none.fl_str_mv Vazquez, Berta N.
Thackray, Joshua K.
Simonet, Nicolás G.
Chahar, Sanjay
Kane-Goldsmith, Noriko
Newkirk, Simon J.
Lee, Suman
Xing, Jinchuan
Verzi, Michael P.
An, Wenfeng
Vaquero García, Alejandro
Tischfield, Jay A.
Serrano, Lourdes
author Vazquez, Berta N.
author_facet Vazquez, Berta N.
Thackray, Joshua K.
Simonet, Nicolás G.
Chahar, Sanjay
Kane-Goldsmith, Noriko
Newkirk, Simon J.
Lee, Suman
Xing, Jinchuan
Verzi, Michael P.
An, Wenfeng
Vaquero García, Alejandro
Tischfield, Jay A.
Serrano, Lourdes
author_role author
author2 Thackray, Joshua K.
Simonet, Nicolás G.
Chahar, Sanjay
Kane-Goldsmith, Noriko
Newkirk, Simon J.
Lee, Suman
Xing, Jinchuan
Verzi, Michael P.
An, Wenfeng
Vaquero García, Alejandro
Tischfield, Jay A.
Serrano, Lourdes
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Regulació genètica
Epigenètica
Cromatina
Genetic regulation
Epigenetics
Chromatin
topic Regulació genètica
Epigenètica
Cromatina
Genetic regulation
Epigenetics
Chromatin
description Long interspersed elements-1 (LINE-1, L1) are retrotransposons that hold the capacity of self-propagation in the genome with potential mutagenic outcomes. How somatic cells restrict L1 activity and how this process becomes dysfunctional during aging and in cancer cells is poorly understood. L1s are enriched at lamin-associated domains, heterochromatic regions of the nuclear periphery. Whether this association is necessary for their repression has been elusive. Here we show that the sirtuin family member SIRT7 participates in the epigenetic transcriptional repression of L1 genome-wide in both mouse and human cells. SIRT7 depletion leads to increased L1 expression and retrotransposition. Mechanistically, we identify a novel interplay between SIRT7 and Lamin A/C in L1 repression. Our results demonstrate that SIRT7-mediated H3K18 deacetylation regulates L1 expression and promotes L1 association with elements of the nuclear lamina. The failure of such activity might contribute to the observed genome instability and compromised viability in SIRT7 knockout mice. Overall, our results reveal a novel function of SIRT7 on chromatin organization by mediating the anchoring of L1 to the nuclear envelope, and a new functional link of the nuclear lamina with transcriptional repression.
publishDate 2019
dc.date.none.fl_str_mv 2019
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 https://hdl.handle.net/2445/171238
url https://hdl.handle.net/2445/171238
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1093/nar/gkz519
Nucleic Acids Research, 2019, vol. 47, num. 15, p. 7870-7885
https://doi.org/10.1093/nar/gkz519
dc.rights.none.fl_str_mv cc by-nc (c) Vazquez et al., 2019
http://creativecommons.org/licenses/by-nc/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc (c) Vazquez et al., 2019
http://creativecommons.org/licenses/by-nc/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 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 Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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