|
| Status |
Public on Feb 15, 2022 |
| Title |
H3K27me3 conditions chemotolerance in triple-negative breast cancer [ChIP-reChIP] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Triple-negative breast cancer is associated with the worst prognosis and the highest risk of recurrence among all breast cancer subtypes1. Residual disease, formed by cancer cells persistent to chemotherapy, remains the major clinical challenge towards full cure2,3. There is now consensus that non-genetic processes contribute to chemoresistance in various tumor types, notably through the initial emergence of a reversible chemotolerant state4–6. Understanding non-genetic tumor evolution stands now as a prerequisite for the design of relevant combinatorial approaches to delay recurrence. Here we show that the repressive histone mark H3K27me3 is a determinant of cell fate under chemotherapy exposure, monitoring epigenomes, transcriptomes and lineage with single-cell resolution. We identify a reservoir of persister basal cells with EMT markers and activated TGF-β pathway leading to multiple chemoresistance phenotypes. We demonstrate that, in unchallenged cells, H3K27 methylation is a lock to the expression program of persister cells. Promoters are primed with both H3K4me3 and H3K27me3, and removing H3K27me3 is sufficient for their transcriptional activation. Leveraging lineage barcoding, we show that depleting H3K27me3 alters tumor cell fate under chemotherapy insult - a wider variety of tumor cells tolerate chemotherapy. Our results highlight how chromatin landscapes shape the potential of unchallenged cancer cells to respond to therapeutic stress and pave the way for combinatorial therapy with modulators of chromatin.
|
| |
|
| Overall design |
Two sequential ChIP-seq samples on untreated MDA-MB-468 cells of H3K27me3 followed byH3K4me3 or H3K27me3 followed by IgG negative control. The ‘primary’ ChIP containing part of the tube before the second immuno-precipation was also sequenced for each sample in order to eliminate background noise. BigWigs of the sequencing ChIPs compared to their respective ‘primary’ ChIP are also present. 8 bulk ChIP-seq MDA-MB-468 cells against H3K27me3 mark treated or not with 5-FU (‘persister’ or ‘DMSO’). 5 demultiplexed chromatin indexing samples from the same pool agaisnt H3K4me3 mark, treated or not with 5-FU.
>>>Raw data not available for patient-derived PDX samples due to privacy concerns<<<
|
| |
|
| Contributor(s) |
Marsolier J, Prompsy P, Durand A, Vallot C |
| Citation(s) |
37340307 |
| |
| Submission date |
Nov 01, 2021 |
| Last update date |
Sep 08, 2023 |
| Contact name |
Céline Vallot |
| E-mail(s) |
celine.vallot@curie.fr
|
| Phone |
0156246340
|
| Organization name |
Institut Curie
|
| Street address |
26 Rue D'Ulm
|
| City |
Paris |
| ZIP/Postal code |
75005 |
| Country |
France |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (23)
|
|
| This SubSeries is part of SuperSeries: |
| GSE164716 |
H3K27me3 conditions chemotolerance in triple-negative breast cancer |
|
| Relations |
| BioProject |
PRJNA776903 |
| SRA |
SRP344095 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE186965_BT20_fisher_pvalue_K4_IgG_peak_1e-30_4.csv.gz |
604.9 Kb |
(ftp)(http) |
CSV |
| GSE186965_BT20_fisher_pvalue_K4_K27_peak_1e-30_4.csv.gz |
527.4 Kb |
(ftp)(http) |
CSV |
| GSE186965_BT20_reChIP_H3K4me3_H3K27me3_vs_BT20_primary_H3K4me3_IgG.bw |
6.7 Mb |
(ftp)(http) |
BW |
| GSE186965_BT20_reChIP_H3K4me3_IgG_vs_BT20_primary_H3K4me3_IgG.bw |
7.7 Mb |
(ftp)(http) |
BW |
| GSE186965_BT20_summits_K4_K27_peak_significant_1e-30_4.bed.gz |
16.1 Kb |
(ftp)(http) |
BED |
| GSE186965_HBCx172_fisher_pvalue_K4_IgG_peak_0.001_4.csv.gz |
719.5 Kb |
(ftp)(http) |
CSV |
| GSE186965_HBCx172_fisher_pvalue_K4_K27_peak_0.001_4.csv.gz |
669.0 Kb |
(ftp)(http) |
CSV |
| GSE186965_HBCx172_reChIP_H3K4me3_H3K27me3_vs_HBCx172_primary_H3K4me3_H3K27me3.bw |
2.2 Mb |
(ftp)(http) |
BW |
| GSE186965_HBCx172_reChIP_H3K4me3_IgG_vs_HBCx172_primary_H3K4me3_IgG.bw |
2.5 Mb |
(ftp)(http) |
BW |
| GSE186965_HBCx172_summits_K4_K27_peak_significant_0.001_4.bed.gz |
33.2 Kb |
(ftp)(http) |
BED |
| GSE186965_HBCx39_fisher_pvalue_K4_IgG_peak_0.001_4.csv.gz |
783.0 Kb |
(ftp)(http) |
CSV |
| GSE186965_HBCx39_fisher_pvalue_K4_K27_peak_0.001_4.csv.gz |
753.1 Kb |
(ftp)(http) |
CSV |
| GSE186965_HBCx39_reChIP_H3K4me3_H3K27me3_vs_HBCx39_primary_H3K4me3_H3K27me3.bw |
3.9 Mb |
(ftp)(http) |
BW |
| GSE186965_HBCx39_reChIP_H3K4me3_IgG_vs_HBCx39_primary_H3K4me3_IgG.bw |
1.1 Mb |
(ftp)(http) |
BW |
| GSE186965_HBCx39_summits_K4_K27_peak_significant_0.001_4.bed.gz |
23.2 Kb |
(ftp)(http) |
BED |
| GSE186965_HBCx95_fisher_pvalue_K4_IgG_peak_1e-15_4.csv.gz |
779.9 Kb |
(ftp)(http) |
CSV |
| GSE186965_HBCx95_fisher_pvalue_K4_K27_peak_1e-15_4.csv.gz |
669.5 Kb |
(ftp)(http) |
CSV |
| GSE186965_HBCx95_reChIP_H3K4me3_H3K27me3_vs_primary_H3K4me3.bw |
12.1 Mb |
(ftp)(http) |
BW |
| GSE186965_HBCx95_reChIP_H3K4me3_IgG_vs_primary_H3K4me3.bw |
13.5 Mb |
(ftp)(http) |
BW |
| GSE186965_HBCx95_summits_K4_K27_peak_significant_1e-15_4.bed.gz |
10.0 Kb |
(ftp)(http) |
BED |
| GSE186965_HCC38_fisher_pvalue_K4_IgG_peak_1e-15_4.csv.gz |
717.1 Kb |
(ftp)(http) |
CSV |
| GSE186965_HCC38_fisher_pvalue_K4_K27_peak_1e-15_4.csv.gz |
667.4 Kb |
(ftp)(http) |
CSV |
| GSE186965_HCC38_reChIP_H3K4me3_H3K27me3_vs_HCC38_primary_H3K4me3_H3K27me3.bw |
11.8 Mb |
(ftp)(http) |
BW |
| GSE186965_HCC38_reChIP_H3K4me3_IgG_vs_HCC38_primary_H3K4me3_IgG.bw |
18.7 Mb |
(ftp)(http) |
BW |
| GSE186965_HCC38_summits_K4_K27_peak_significant_1e-15_4.bed.gz |
9.8 Kb |
(ftp)(http) |
BED |
| GSE186965_MM468_fisher_pvalue_K4_IgG_peak_0.001_4.csv.gz |
609.0 Kb |
(ftp)(http) |
CSV |
| GSE186965_MM468_fisher_pvalue_K4_K27_peak_0.001_4.csv.gz |
543.6 Kb |
(ftp)(http) |
CSV |
| GSE186965_MM468_reChIP_H3K4me3_H3K27me3_vs_MM468_primary_H3K4me3_H3K27me3.bw |
5.3 Mb |
(ftp)(http) |
BW |
| GSE186965_MM468_reChIP_H3K4me3_IgG_vs_MM468_primary_H3K4me3_IgG.bw |
2.8 Mb |
(ftp)(http) |
BW |
| GSE186965_MM468_summits_K4_K27_peak_significant_0.001_4.bed.gz |
18.5 Kb |
(ftp)(http) |
BED |
| GSE186965_RAW.tar |
3.0 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
Less...
More...