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| Status |
Public on Aug 06, 2024 |
| Title |
Deterioration of multi-level 3D genome organization during breast cancer progression [third-party re-analysis] |
| Sample organism |
Homo sapiens |
| Experiment type |
Third-party reanalysis
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Breast cancer progression entails intricate, multi-level alterations in genome organization and expression. To gain insights into the modifications in chromatin's three-dimensional (3D) structure during breast cancer progression, we conducted an analysis combining Hi-C data with lamina-associated domains (LADs), epigenomic marks, and gene expression in an in vitro model of breast cancer progression. Our results reveal that while the fundamental properties of topologically associating domains (TADs) remain largely stable, significant changes occur in the organization of compartments and subcompartments. These changes are closely correlated with alterations in the expression of oncogenic genes. We also observed a restructuring of TAD-TAD interactions, coinciding with a loss of spatial compartmentalization and radial positioning of the 3D genome. Notably, we identified a previously unrecognized interchromosomal insertion event, wherein a locus on chromosome 8 housing the MYC oncogene becomes inserted into a highly active region on chromosome 10. This insertion event leads to the formation of de novo enhancer contacts and activation of the oncogene, illustrating how structural variants can interact with the 3D genome to drive oncogenic states. In summary, our findings provide evidence for the degradation of genome organization at multiple scales during breast cancer progression revealing the complex interplay between genomic structure and oncogenic processes.
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| Overall design |
We reanalyzed publicly available ChIP-seq datasets (CTCF, H2AZ, H3K9ac, H3K9me3, H3K27ac, H3K4me3, H3K27me3, H3K79me2, gH2AX, p53) for MCF10A, MCF10AT1 and MCF10Ca1a to compare chromatin states with our subcompartment annotation (GSE246947) (note that not all experiments included dataset for MCF10AT1 and MCF10Ca1a).
The re-analyzed samples are from GSE85158, GSE93757, GSE98551, GSE100234, GSE109721, GSE134297, GSE140252, and GSE181524 Series records.
The sample titles and their GEO, SRA, biosample accessions are provided in the 're-analyzed_sample_accns.txt' and the processed data file associated with each sample is listed in the 'sample_to_processed-data-file.txt'
**Re-analysis data processing step:
nf-core/chipseq v2.0.0
Samples were processed using nf-core/chipseq after collapsing replicates.
hg38 and Gencode v43 were used as reference genome assemby and gene annotation, respectively.
The effective genome size for MACS2 provided to the pipelien through the –macs_gsize option was computed using unique-kmers.py from khmer v2.1.1.
Peaks for transcription factors were called in narrow peak mode, while the rest of the peaks were called in broad peak mode.
**processed data files format and content:
BigWig files contain ChIP coverage scaled to 1 million mapped reads. Files containing coverage for background (control) are suffixed with “_input”.
Files in narrowPeak and broadPeak format contain the peaks called with MACS2.
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| Contributor(s) |
Rossini R, Oshaghi M, Nekrasov M, Bellanger A, Domaschenz R, Dijkwel Y, Collas P, Tremethick D, Paulsen J |
| Citation(s) |
38076897 |
| |
| Submission date |
Nov 07, 2023 |
| Last update date |
Aug 06, 2024 |
| Contact name |
Roberto Rossini |
| Organization name |
University of Oslo
|
| Street address |
Blindernveien 31
|
| City |
Oslo |
| ZIP/Postal code |
0371 |
| Country |
Norway |
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| Relations |
| Reanalysis of |
GSM2258716 |
| Reanalysis of |
GSM2258717 |
| Reanalysis of |
GSM2258720 |
| Reanalysis of |
GSM2258721 |
| Reanalysis of |
GSM2461669 |
| Reanalysis of |
GSM2461674 |
| Reanalysis of |
GSM2599084 |
| Reanalysis of |
GSM2599085 |
| Reanalysis of |
GSM2599086 |
| Reanalysis of |
GSM2599087 |
| Reanalysis of |
GSM2599088 |
| Reanalysis of |
GSM2599089 |
| Reanalysis of |
GSM2599090 |
| Reanalysis of |
GSM2599091 |
| Reanalysis of |
GSM2599092 |
| Reanalysis of |
GSM2675538 |
| Reanalysis of |
GSM2675539 |
| Reanalysis of |
GSM2949413 |
| Reanalysis of |
GSM2949414 |
| Reanalysis of |
GSM2949415 |
| Reanalysis of |
GSM2949416 |
| Reanalysis of |
GSM3941584 |
| Reanalysis of |
GSM3941585 |
| Reanalysis of |
GSM3941586 |
| Reanalysis of |
GSM3941587 |
| Reanalysis of |
GSM3941588 |
| Reanalysis of |
GSM3941589 |
| Reanalysis of |
GSM3941590 |
| Reanalysis of |
GSM3941591 |
| Reanalysis of |
GSM3941604 |
| Reanalysis of |
GSM3941605 |
| Reanalysis of |
GSM3941606 |
| Reanalysis of |
GSM3941607 |
| Reanalysis of |
GSM3941608 |
| Reanalysis of |
GSM3941609 |
| Reanalysis of |
GSM3941610 |
| Reanalysis of |
GSM3941611 |
| Reanalysis of |
GSM4158376 |
| Reanalysis of |
GSM4158377 |
| Reanalysis of |
GSM4158378 |
| Reanalysis of |
GSM4158379 |
| Reanalysis of |
GSM5504430 |
| Reanalysis of |
GSM5504431 |
| Reanalysis of |
GSM5504432 |
| Reanalysis of |
GSM5504433 |
| Reanalysis of |
GSM5504434 |
| Reanalysis of |
GSM5504435 |
| Reanalysis of |
GSM5504436 |
| Reanalysis of |
GSM5504437 |
| Reanalysis of |
GSM5504442 |
| Reanalysis of |
GSM5504443 |
| Reanalysis of |
GSM5504444 |
| Reanalysis of |
GSM5504445 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE247171_MCF10A_C1_CTCF.bigWig |
544.6 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_C1_CTCF_input.bigWig |
290.9 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_C1_CTCF_peaks.narrowPeak.gz |
963.9 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE247171_MCF10A_C1_H2AZ_HIGH.bigWig |
112.9 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_C1_H2AZ_HIGH_input.bigWig |
67.7 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_C1_H2AZ_HIGH_peaks.broadPeak.gz |
351.1 Kb |
(ftp)(http) |
BROADPEAK |
| GSE247171_MCF10A_C1_H2AZ_LOW.bigWig |
19.5 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_C1_H2AZ_LOW_input.bigWig |
43.4 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_C1_H2AZ_LOW_peaks.broadPeak.gz |
133.5 Kb |
(ftp)(http) |
BROADPEAK |
| GSE247171_MCF10A_C1_H3K27ac.bigWig |
322.5 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_C1_H3K27ac_input.bigWig |
91.0 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_C1_H3K27ac_peaks.broadPeak.gz |
724.7 Kb |
(ftp)(http) |
BROADPEAK |
| GSE247171_MCF10A_T1_CTCF.bigWig |
477.4 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_T1_CTCF_input.bigWig |
290.9 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_T1_CTCF_peaks.narrowPeak.gz |
1.1 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE247171_MCF10A_T1_H3K27ac.bigWig |
311.6 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_T1_H3K27ac_input.bigWig |
163.4 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_T1_H3K27ac_peaks.broadPeak.gz |
620.5 Kb |
(ftp)(http) |
BROADPEAK |
| GSE247171_MCF10A_WT_CTCF.bigWig |
419.4 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_CTCF_input.bigWig |
436.3 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_CTCF_peaks.narrowPeak.gz |
1.4 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE247171_MCF10A_WT_H2AZ_HIGH.bigWig |
76.1 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_H2AZ_HIGH_input.bigWig |
100.3 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_H2AZ_HIGH_peaks.broadPeak.gz |
288.8 Kb |
(ftp)(http) |
BROADPEAK |
| GSE247171_MCF10A_WT_H2AZ_LOW.bigWig |
22.3 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_H2AZ_LOW_input.bigWig |
49.3 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_H2AZ_LOW_peaks.broadPeak.gz |
116.8 Kb |
(ftp)(http) |
BROADPEAK |
| GSE247171_MCF10A_WT_H3K27ac.bigWig |
188.2 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_H3K27ac_input.bigWig |
136.5 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_H3K27ac_peaks.broadPeak.gz |
873.7 Kb |
(ftp)(http) |
BROADPEAK |
| GSE247171_MCF10A_WT_H3K27me3.bigWig |
218.5 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_H3K27me3_input.bigWig |
238.5 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_H3K27me3_peaks.broadPeak.gz |
1.1 Mb |
(ftp)(http) |
BROADPEAK |
| GSE247171_MCF10A_WT_H3K4me3.bigWig |
178.8 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_H3K4me3_input.bigWig |
238.5 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_H3K4me3_peaks.broadPeak.gz |
1.0 Mb |
(ftp)(http) |
BROADPEAK |
| GSE247171_MCF10A_WT_H3K79me2.bigWig |
209.1 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_H3K79me2_input.bigWig |
238.5 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_H3K79me2_peaks.broadPeak.gz |
1.8 Mb |
(ftp)(http) |
BROADPEAK |
| GSE247171_MCF10A_WT_H3K9ac.bigWig |
565.9 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_H3K9ac_input.bigWig |
659.8 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_H3K9ac_peaks.broadPeak.gz |
4.2 Mb |
(ftp)(http) |
BROADPEAK |
| GSE247171_MCF10A_WT_H3K9me3.bigWig |
94.4 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_H3K9me3_input.bigWig |
317.5 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_H3K9me3_peaks.broadPeak.gz |
1.7 Mb |
(ftp)(http) |
BROADPEAK |
| GSE247171_MCF10A_WT_gH2AX.bigWig |
433.5 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_gH2AX_input.bigWig |
377.7 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_gH2AX_peaks.broadPeak.gz |
37.8 Kb |
(ftp)(http) |
BROADPEAK |
| GSE247171_MCF10A_WT_p53.bigWig |
432.1 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_p53_input.bigWig |
503.8 Mb |
(ftp)(http) |
BIGWIG |
| GSE247171_MCF10A_WT_p53_peaks.narrowPeak.gz |
50.6 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE247171_re-analyzed_sample_accns.txt.gz |
1014 b |
(ftp)(http) |
TXT |
| GSE247171_sample_to_processed-data-file.txt.gz |
622 b |
(ftp)(http) |
TXT |
