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SETDB1 fuels the lung cancer phenotype by modulating epigenome, 3D genome organization and chromatin mechanical properties

Imbalance in the finely orchestrated system of chromatin-modifying enzymes is a hallmark of many pathologies such as cancers, since causing the affection of the epigenome and transcriptional reprogramming. Here, we demonstrate that a loss-of-function mutation (LOF) of the major histone lysine methyl...

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Autores principales: Zakharova, Vlada V, Magnitov, Mikhail D, Del Maestro, Laurence, Ulianov, Sergey V, Glentis, Alexandros, Uyanik, Burhan, Williart, Alice, Karpukhina, Anna, Demidov, Oleg, Joliot, Veronique, Vassetzky, Yegor S, Mège, René-Marc, Piel, Matthieu, Razin, Sergey V, Ait-Si-Ali, Slimane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071401/
https://www.ncbi.nlm.nih.gov/pubmed/35474385
http://dx.doi.org/10.1093/nar/gkac234
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author Zakharova, Vlada V
Magnitov, Mikhail D
Del Maestro, Laurence
Ulianov, Sergey V
Glentis, Alexandros
Uyanik, Burhan
Williart, Alice
Karpukhina, Anna
Demidov, Oleg
Joliot, Veronique
Vassetzky, Yegor S
Mège, René-Marc
Piel, Matthieu
Razin, Sergey V
Ait-Si-Ali, Slimane
author_facet Zakharova, Vlada V
Magnitov, Mikhail D
Del Maestro, Laurence
Ulianov, Sergey V
Glentis, Alexandros
Uyanik, Burhan
Williart, Alice
Karpukhina, Anna
Demidov, Oleg
Joliot, Veronique
Vassetzky, Yegor S
Mège, René-Marc
Piel, Matthieu
Razin, Sergey V
Ait-Si-Ali, Slimane
author_sort Zakharova, Vlada V
collection PubMed
description Imbalance in the finely orchestrated system of chromatin-modifying enzymes is a hallmark of many pathologies such as cancers, since causing the affection of the epigenome and transcriptional reprogramming. Here, we demonstrate that a loss-of-function mutation (LOF) of the major histone lysine methyltransferase SETDB1 possessing oncogenic activity in lung cancer cells leads to broad changes in the overall architecture and mechanical properties of the nucleus through genome-wide redistribution of heterochromatin, which perturbs chromatin spatial compartmentalization. Together with the enforced activation of the epithelial expression program, cytoskeleton remodeling, reduced proliferation rate and restricted cellular migration, this leads to the reversed oncogenic potential of lung adenocarcinoma cells. These results emphasize an essential role of chromatin architecture in the determination of oncogenic programs and illustrate a relationship between gene expression, epigenome, 3D genome and nuclear mechanics.
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spelling pubmed-90714012022-05-06 SETDB1 fuels the lung cancer phenotype by modulating epigenome, 3D genome organization and chromatin mechanical properties Zakharova, Vlada V Magnitov, Mikhail D Del Maestro, Laurence Ulianov, Sergey V Glentis, Alexandros Uyanik, Burhan Williart, Alice Karpukhina, Anna Demidov, Oleg Joliot, Veronique Vassetzky, Yegor S Mège, René-Marc Piel, Matthieu Razin, Sergey V Ait-Si-Ali, Slimane Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Imbalance in the finely orchestrated system of chromatin-modifying enzymes is a hallmark of many pathologies such as cancers, since causing the affection of the epigenome and transcriptional reprogramming. Here, we demonstrate that a loss-of-function mutation (LOF) of the major histone lysine methyltransferase SETDB1 possessing oncogenic activity in lung cancer cells leads to broad changes in the overall architecture and mechanical properties of the nucleus through genome-wide redistribution of heterochromatin, which perturbs chromatin spatial compartmentalization. Together with the enforced activation of the epithelial expression program, cytoskeleton remodeling, reduced proliferation rate and restricted cellular migration, this leads to the reversed oncogenic potential of lung adenocarcinoma cells. These results emphasize an essential role of chromatin architecture in the determination of oncogenic programs and illustrate a relationship between gene expression, epigenome, 3D genome and nuclear mechanics. Oxford University Press 2022-04-26 /pmc/articles/PMC9071401/ /pubmed/35474385 http://dx.doi.org/10.1093/nar/gkac234 Text en © The Author(s) 2022. 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 (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
Zakharova, Vlada V
Magnitov, Mikhail D
Del Maestro, Laurence
Ulianov, Sergey V
Glentis, Alexandros
Uyanik, Burhan
Williart, Alice
Karpukhina, Anna
Demidov, Oleg
Joliot, Veronique
Vassetzky, Yegor S
Mège, René-Marc
Piel, Matthieu
Razin, Sergey V
Ait-Si-Ali, Slimane
SETDB1 fuels the lung cancer phenotype by modulating epigenome, 3D genome organization and chromatin mechanical properties
title SETDB1 fuels the lung cancer phenotype by modulating epigenome, 3D genome organization and chromatin mechanical properties
title_full SETDB1 fuels the lung cancer phenotype by modulating epigenome, 3D genome organization and chromatin mechanical properties
title_fullStr SETDB1 fuels the lung cancer phenotype by modulating epigenome, 3D genome organization and chromatin mechanical properties
title_full_unstemmed SETDB1 fuels the lung cancer phenotype by modulating epigenome, 3D genome organization and chromatin mechanical properties
title_short SETDB1 fuels the lung cancer phenotype by modulating epigenome, 3D genome organization and chromatin mechanical properties
title_sort setdb1 fuels the lung cancer phenotype by modulating epigenome, 3d genome organization and chromatin mechanical properties
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071401/
https://www.ncbi.nlm.nih.gov/pubmed/35474385
http://dx.doi.org/10.1093/nar/gkac234
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