Compartmental reorganization suppresses tumours

Autor: Noam Shoresh, Yifeng Qi, Esmat Hegazi, Sowmya Iyer, Luli S. Zou, Nir Hacohen, Bin Zhang, Vivian Hecht, Martin K. Selig, Caleb A. Lareau, Yotam Drier, Rafael A. Irizarry, Eric F. Joyce, Karin Pelka, Bradley E. Bernstein, Son C. Nguyen, Jonathan H. Chen, Martin J. Aryee, Alejandro Reyes, Sarah E. Johnstone, Carmen Adriaens
Rok vydání: 2020
Předmět:
Epigenomics
Colorectal cancer
Biology
Molecular Dynamics Simulation
Topology
medicine.disease_cause
Genome
behavioral disciplines and activities
Article
General Biochemistry
Genetics and Molecular Biology
Chromosomes
Epigenesis
Genetic
Cohort Studies
03 medical and health sciences
0302 clinical medicine
Microscopy
Electron
Transmission
Compartment (development)
Humans
Medicine
Epigenetics
RNA-Seq
Gene
Cellular Senescence
In Situ Hybridization
Fluorescence
030304 developmental biology
0303 health sciences
Spatial Analysis
business.industry
Tumor Suppressor Proteins
Cancer
Computational Biology
DNA Methylation
HCT116 Cells
medicine.disease
Chromatin
Gene Expression Regulation
Neoplastic
030220 oncology & carcinogenesis
DNA methylation
Disease Progression
Cancer research
Chromatin Immunoprecipitation Sequencing
Colorectal Neoplasms
business
Carcinogenesis
030217 neurology & neurosurgery
Cell Division
Zdroj: Cell
ISSN: 1474-1768
1474-175X
Popis: Widespread changes to DNA methylation and chromatin are well documented in cancer, but the fate of higher-order chromosomal structure remains obscure. Here we integrated topological maps for colon tumors and normal colons with epigenetic, transcriptional, and imaging data to characterize alterations to chromatin loops, topologically associated domains, and large-scale compartments. We found that spatial partitioning of the open and closed genome compartments is profoundly compromised in tumors. This reorganization is accompanied by compartment-specific hypomethylation and chromatin changes. Additionally, we identify a compartment at the interface between the canonical A and B compartments that is reorganized in tumors. Remarkably, similar shifts were evident in non-malignant cells that have accumulated excess divisions. Our analyses suggest that these topological changes repress stemness and invasion programs while inducing anti-tumor immunity genes and may therefore restrain malignant progression. Our findings call into question the conventional view that tumor-associated epigenomic alterations are primarily oncogenic.
Databáze: OpenAIRE
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