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| Pàgina inicial > Articles > Articles publicats > SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina |
(Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Department of Genetics. Human Genetics Institute of New Jersey. Rutgers University) (Department of Pharmaceutical Sciences. College of Pharmacy and Allied Health Professions. South Dakota State University) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)| Data: | 2019 |
| Resum: | 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. |
| Ajuts: | Ministerio de Educación, Cultura y Deporte EX-2010-278 Ministerio de Educación, Cultura y Deporte BES-2012-052200 Ministerio de Economía y Competitividad SAF2014-55964-R Ministerio de Economía y Competitividad SAF2017-88975-R |
| Nota: | Altres ajuts: La Marató de TV3. |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Animals ; Cell Line ; Cell Line, Tumor ; Chromatin Immunoprecipitation ; Epigenesis, Genetic ; Fibroblasts ; Genome ; Heterochromatin ; Histones ; Humans ; K562 Cells ; Lamin Type A ; Liver ; Long Interspersed Nucleotide Elements ; Male ; Mice ; Mice, Knockout ; Myocardium ; Nuclear Lamina ; Sirtuins ; Testis ; Transcription, Genetic |
| Publicat a: | Nucleic acids research, Vol. 47 Núm. 15 (january 2019) , p. 7870-7885, ISSN 1362-4962 |
