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SETDB1 Fuels the Lung Cancer Phenotype by Modulating Epigenome, 3D Genome Organization and Chromatin Mechanical Properties
- Publication Year :
- 2021
- Publisher :
- Cold Spring Harbor Laboratory, 2021.
-
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.
- Subjects :
- Lung Neoplasms
Heterochromatin
[SDV]Life Sciences [q-bio]
Biology
medicine.disease_cause
Epigenome
03 medical and health sciences
0302 clinical medicine
Gene expression
Genetics
medicine
Humans
030304 developmental biology
0303 health sciences
Mutation
Cell migration
Histone-Lysine N-Methyltransferase
Phenotype
Chromatin
Cell biology
030220 oncology & carcinogenesis
Reprogramming
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....aec1e1684654bd7cd8dc331a432726c5