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Title: SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina
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 García, Alejandro
Tischfield, Jay A.
Serrano, Lourdes
Keywords: Regulació genètica
Genetic regulation
Issue Date: 5-Jan-2019
Publisher: Oxford University Press
Abstract: 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.
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It is part of: Nucleic Acids Research, 2019, vol. 47, num. 15, p. 7870-7885
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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