SETDB1 fuels the lung cancer phenotype by modulating epigenome, 3D genome organization and chromatin mechanical properties - Institut Jacques Monod Access content directly
Journal Articles Nucleic Acids Research Year : 2022

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

Mikhail Magnitov
  • Function : Author
Sergey Ulianov
Burhan Uyanik
  • Function : Author
René-Marc Mège
Sergey V Razin

Abstract

Abstract 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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Dates and versions

hal-03781895 , version 1 (18-11-2022)

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Vlada Zakharova, Mikhail Magnitov, Laurence del Maestro, Sergey Ulianov, Alexandros Glentis, et al.. SETDB1 fuels the lung cancer phenotype by modulating epigenome, 3D genome organization and chromatin mechanical properties. Nucleic Acids Research, 2022, 50 (8), pp.4389-4413. ⟨10.1093/nar/gkac234⟩. ⟨hal-03781895⟩
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