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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735864/ https://www.ncbi.nlm.nih.gov/pubmed/31226208 http://dx.doi.org/10.1093/nar/gkz519 |
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author | Vazquez, Berta N Thackray, Joshua K Simonet, Nicolas G Chahar, Sanjay Kane-Goldsmith, Noriko Newkirk, Simon J Lee, Suman Xing, Jinchuan Verzi, Michael P An, Wenfeng Vaquero, Alejandro Tischfield, Jay A Serrano, Lourdes |
author_facet | Vazquez, Berta N Thackray, Joshua K Simonet, Nicolas G Chahar, Sanjay Kane-Goldsmith, Noriko Newkirk, Simon J Lee, Suman Xing, Jinchuan Verzi, Michael P An, Wenfeng Vaquero, Alejandro Tischfield, Jay A Serrano, Lourdes |
author_sort | Vazquez, Berta N |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-6735864 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-67358642019-09-16 SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina Vazquez, Berta N Thackray, Joshua K Simonet, Nicolas G Chahar, Sanjay Kane-Goldsmith, Noriko Newkirk, Simon J Lee, Suman Xing, Jinchuan Verzi, Michael P An, Wenfeng Vaquero, Alejandro Tischfield, Jay A Serrano, Lourdes Nucleic Acids Res Gene regulation, Chromatin and Epigenetics 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. Oxford University Press 2019-09-05 2019-06-21 /pmc/articles/PMC6735864/ /pubmed/31226208 http://dx.doi.org/10.1093/nar/gkz519 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Gene regulation, Chromatin and Epigenetics Vazquez, Berta N Thackray, Joshua K Simonet, Nicolas G Chahar, Sanjay Kane-Goldsmith, Noriko Newkirk, Simon J Lee, Suman Xing, Jinchuan Verzi, Michael P An, Wenfeng Vaquero, Alejandro Tischfield, Jay A Serrano, Lourdes 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 |
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_short | 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 |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735864/ https://www.ncbi.nlm.nih.gov/pubmed/31226208 http://dx.doi.org/10.1093/nar/gkz519 |
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