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The splicing regulator SLU7 is required to preserve DNMT1 protein stability and DNA methylation
Gene expression is finely and dynamically controlled through the tightly coordinated and interconnected activity of epigenetic modulators, transcription and splicing factors and post-translational modifiers. We have recently identified the splicing factor SLU7 as essential for maintaining liver cell...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421144/ https://www.ncbi.nlm.nih.gov/pubmed/34331453 http://dx.doi.org/10.1093/nar/gkab649 |
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author | Recalde, Miriam Gárate-Rascón, María Elizalde, María Azkona, María Latasa, M Ujue Bárcena-Varela, Marina Sangro, Bruno Fernández-Barrena, Maite G Ávila, Matías A Arechederra, María Berasain, Carmen |
author_facet | Recalde, Miriam Gárate-Rascón, María Elizalde, María Azkona, María Latasa, M Ujue Bárcena-Varela, Marina Sangro, Bruno Fernández-Barrena, Maite G Ávila, Matías A Arechederra, María Berasain, Carmen |
author_sort | Recalde, Miriam |
collection | PubMed |
description | Gene expression is finely and dynamically controlled through the tightly coordinated and interconnected activity of epigenetic modulators, transcription and splicing factors and post-translational modifiers. We have recently identified the splicing factor SLU7 as essential for maintaining liver cell identity and genome integrity and for securing cell division both trough transcriptional and splicing mechanisms. Now we uncover a new function of SLU7 controlling gene expression at the epigenetic level. We show that SLU7 is required to secure DNMT1 protein stability and a correct DNA methylation. We demonstrate that SLU7 is part in the chromatome of the protein complex implicated in DNA methylation maintenance interacting with and controlling the integrity of DNMT1, its adaptor protein UHRF1 and the histone methyl-transferase G9a at the chromatin level. Mechanistically, we found that SLU7 assures DNMT1 stability preventing its acetylation and degradation by facilitating its interaction with HDAC1 and the desubiquitinase USP7. Importantly, we demonstrate that this DNMT1 dependency on SLU7 occurs in a large panel of proliferating cell lines of different origins and in in vivo models of liver proliferation. Overall, our results uncover a novel and non-redundant role of SLU7 in DNA methylation and present SLU7 as a holistic regulator of gene expression. |
format | Online Article Text |
id | pubmed-8421144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-84211442021-09-09 The splicing regulator SLU7 is required to preserve DNMT1 protein stability and DNA methylation Recalde, Miriam Gárate-Rascón, María Elizalde, María Azkona, María Latasa, M Ujue Bárcena-Varela, Marina Sangro, Bruno Fernández-Barrena, Maite G Ávila, Matías A Arechederra, María Berasain, Carmen Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Gene expression is finely and dynamically controlled through the tightly coordinated and interconnected activity of epigenetic modulators, transcription and splicing factors and post-translational modifiers. We have recently identified the splicing factor SLU7 as essential for maintaining liver cell identity and genome integrity and for securing cell division both trough transcriptional and splicing mechanisms. Now we uncover a new function of SLU7 controlling gene expression at the epigenetic level. We show that SLU7 is required to secure DNMT1 protein stability and a correct DNA methylation. We demonstrate that SLU7 is part in the chromatome of the protein complex implicated in DNA methylation maintenance interacting with and controlling the integrity of DNMT1, its adaptor protein UHRF1 and the histone methyl-transferase G9a at the chromatin level. Mechanistically, we found that SLU7 assures DNMT1 stability preventing its acetylation and degradation by facilitating its interaction with HDAC1 and the desubiquitinase USP7. Importantly, we demonstrate that this DNMT1 dependency on SLU7 occurs in a large panel of proliferating cell lines of different origins and in in vivo models of liver proliferation. Overall, our results uncover a novel and non-redundant role of SLU7 in DNA methylation and present SLU7 as a holistic regulator of gene expression. Oxford University Press 2021-07-31 /pmc/articles/PMC8421144/ /pubmed/34331453 http://dx.doi.org/10.1093/nar/gkab649 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://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 Recalde, Miriam Gárate-Rascón, María Elizalde, María Azkona, María Latasa, M Ujue Bárcena-Varela, Marina Sangro, Bruno Fernández-Barrena, Maite G Ávila, Matías A Arechederra, María Berasain, Carmen The splicing regulator SLU7 is required to preserve DNMT1 protein stability and DNA methylation |
title | The splicing regulator SLU7 is required to preserve DNMT1 protein stability and DNA methylation |
title_full | The splicing regulator SLU7 is required to preserve DNMT1 protein stability and DNA methylation |
title_fullStr | The splicing regulator SLU7 is required to preserve DNMT1 protein stability and DNA methylation |
title_full_unstemmed | The splicing regulator SLU7 is required to preserve DNMT1 protein stability and DNA methylation |
title_short | The splicing regulator SLU7 is required to preserve DNMT1 protein stability and DNA methylation |
title_sort | splicing regulator slu7 is required to preserve dnmt1 protein stability and dna methylation |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421144/ https://www.ncbi.nlm.nih.gov/pubmed/34331453 http://dx.doi.org/10.1093/nar/gkab649 |
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