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| Status |
Public on Mar 29, 2022 |
| Title |
SETDB1 Fuels the Lung Cancer Phenotype by Modulating Epigenome, 3D Genome Organization, and Chromatin Mechanical Properties |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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 of the major histone lysine methyltransferases SETDB1 possessing oncogenic activity in lung cancer cells leads to broad changes in the overall architecture and mechanical properties of the nucleus through redistribution of heterochromatin genome-wide, 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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| Overall design |
This submission contains RNA-seq, H3K9me3 ChIP-seq, H3K27me3 ChIP-seq, H3K27ac ChIP-seq, H3K4me3 ChIP-seq, CTCF ChIP-seq, and Hi-C experiments on Control (CT) and SETDB1 loss-of-function mutation (KO) A549 cells.
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| Contributor(s) |
Magnitov MD, Zakharova VV, Ait-Si-Ali S |
| Citation(s) |
35474385 |
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| Submission date |
Mar 04, 2021 |
| Last update date |
Nov 22, 2023 |
| Contact name |
Mikhail Magnitov |
| Organization name |
The Netherlands Cancer Institute
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| Street address |
Plesmanlaan 121
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| City |
Amsterdam |
| ZIP/Postal code |
1066CX |
| Country |
Netherlands |
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| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (40)
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| Relations |
| BioProject |
PRJNA706646 |
| SRA |
SRP310732 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE168233_CTCF_CT.bw |
349.7 Mb |
(ftp)(http) |
BW |
| GSE168233_CTCF_CT_peaks.bed.gz |
196.9 Kb |
(ftp)(http) |
BED |
| GSE168233_CTCF_KO.bw |
339.5 Mb |
(ftp)(http) |
BW |
| GSE168233_CTCF_KO_peaks.bed.gz |
282.0 Kb |
(ftp)(http) |
BED |
| GSE168233_H3K27ac_CT.bw |
325.1 Mb |
(ftp)(http) |
BW |
| GSE168233_H3K27ac_CT_peaks.bed.gz |
461.0 Kb |
(ftp)(http) |
BED |
| GSE168233_H3K27ac_KO.bw |
308.5 Mb |
(ftp)(http) |
BW |
| GSE168233_H3K27ac_KO_peaks.bed.gz |
488.6 Kb |
(ftp)(http) |
BED |
| GSE168233_H3K27me3_CT.bw |
293.6 Mb |
(ftp)(http) |
BW |
| GSE168233_H3K27me3_CT_peaks.bed.gz |
751.6 Kb |
(ftp)(http) |
BED |
| GSE168233_H3K27me3_KO.bw |
283.5 Mb |
(ftp)(http) |
BW |
| GSE168233_H3K27me3_KO_peaks.bed.gz |
562.6 Kb |
(ftp)(http) |
BED |
| GSE168233_H3K4me3_CT.bw |
282.7 Mb |
(ftp)(http) |
BW |
| GSE168233_H3K4me3_CT_peaks.bed.gz |
474.9 Kb |
(ftp)(http) |
BED |
| GSE168233_H3K4me3_KO.bw |
265.1 Mb |
(ftp)(http) |
BW |
| GSE168233_H3K4me3_KO_peaks.bed.gz |
577.0 Kb |
(ftp)(http) |
BED |
| GSE168233_H3K9me3_CT.bw |
364.8 Mb |
(ftp)(http) |
BW |
| GSE168233_H3K9me3_CT_peaks.bed.gz |
862.4 Kb |
(ftp)(http) |
BED |
| GSE168233_H3K9me3_KO.bw |
330.2 Mb |
(ftp)(http) |
BW |
| GSE168233_H3K9me3_KO_peaks.bed.gz |
456.9 Kb |
(ftp)(http) |
BED |
| GSE168233_HiC_CT.mcool |
1.3 Gb |
(ftp)(http) |
MCOOL |
| GSE168233_HiC_KO.mcool |
1.4 Gb |
(ftp)(http) |
MCOOL |
| GSE168233_RAW.tar |
8.7 Gb |
(http)(custom) |
TAR (of BW, MCOOL) |
| GSE168233_RNAseq_CT.bw |
57.1 Mb |
(ftp)(http) |
BW |
| GSE168233_RNAseq_KO.bw |
59.8 Mb |
(ftp)(http) |
BW |
| GSE168233_TADs_CT.bed.gz |
31.5 Kb |
(ftp)(http) |
BED |
| GSE168233_TADs_KO.bed.gz |
32.3 Kb |
(ftp)(http) |
BED |
| GSE168233_compartment_signal.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
| GSE168233_gene_counts.txt.gz |
610.9 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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