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| Status |
Public on Apr 17, 2024 |
| Title |
Nucleosome reorganisation in breast cancer tissues |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Background
Nucleosome repositioning in cancer is believed to cause many changes in genome organisation and gene expression. Understanding these changes is important to elucidate fundamental aspects of cancer. It is also important for medical diagnostics based on cell-free DNA (cfDNA), which originates from genomic DNA regions protected from digestion by nucleosomes.
Results
We have generated high-resolution nucleosome maps in paired tumour and normal tissues from the same breast cancer patients using MNase-assisted histone H3 ChIP-seq and compared them with the corresponding cfDNA from blood plasma. This analysis has detected single-nucleosome repositioning at key regulatory regions in a patient-specific manner and common cancer-specific patterns across patients. The nucleosomes gained in tumour versus normal tissue were particularly informative of cancer pathways, with ~ 20-fold enrichment at CpG islands, a large fraction of which marked promoters of genes encoding DNA-binding proteins. The tumour tissues were characterised by a 5–10 bp decrease in the average distance between nucleosomes (nucleosome repeat length, NRL), which is qualitatively similar to the differences between pluripotent and differentiated cells. This effect was correlated with gene activity, differential DNA methylation and changes in local occupancy of linker histone variants H1.4 and H1X.
Conclusions
Our study offers a novel resource of high-resolution nucleosome maps in breast cancer patients and reports for the first time the effect of systematic decrease of NRL in paired tumour versus normal breast tissues from the same patient. Our findings provide a new mechanistic understanding of nucleosome repositioning in tumour tissues that can be valuable for patient diagnostics, stratification and monitoring.
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| Overall design |
MNase-assisted DNA-sequencing (MNase-seq) breast tissues from Breast Cancer patients paired with normal surrounding tissue. In addition, MNase- assisted Chromatin Immunoprecipitation DNA-sequencing (ChIP-seq) for histone variants H3 as well as cell-free DNA sequencing obtained from the same patients' blood plasma.
**RAW data not available due to patient privacy concerns**
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| Contributor(s) |
Jacob DR, Guiblet WM, Mamayusupova H, Shtumpf M, Ruje L, Gretton S, Ciuta I, Bikova M, Correa C, Dellow E, Agrawal SP, Shafiei N, Drobysevskaja A, Armstrong CM, Lam JG, Vainshtein Y, Clarkson CT, Thorn GJ, Sohn K, Pradeepa MM, Apte A, Chandrasekharan S, Brooke G, Klenova E, Zhurkin VB, Teif VB |
| Citation(s) |
38561804 |
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| Submission date |
Aug 01, 2022 |
| Last update date |
Apr 18, 2024 |
| Contact name |
Vladimir B Teif |
| E-mail(s) |
vteif@essex.ac.uk
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| Organization name |
University of Essex
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| Department |
School of Life Sciences
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| Street address |
Wivenhoe Park
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| City |
Colchester |
| ZIP/Postal code |
CO4 3SQ |
| Country |
United Kingdom |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (17)
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| GSM6424685 |
BRC patient P1, cfDNA rep1 |
| GSM6424686 |
BRC patient P1, normal breast tissue, MNase-assisted H3 ChIP-seq |
| GSM6424687 |
BRC patient P1, normal breast tissue, MNase-seq |
| GSM6424688 |
BRC patient P1, tumour breast tissue, MNase-assisted H3 ChIP-seq |
| GSM6424689 |
BRC patient P1, tumour breast tissue, MNase-seq |
| GSM6424690 |
BRC patient P2, normal breast tissue, MNase-seq |
| GSM6424691 |
BRC patient P2, tumour breast tissue, MNase-seq |
| GSM6424692 |
BRC patient P3, cfDNA rep1 |
| GSM6424693 |
BRC patient P3, cfDNA rep2 |
| GSM6424694 |
BRC patient P3, normal breast tissue, MNase-assisted H3 ChIP-seq |
| GSM6424695 |
BRC patient P3, normal breast tissue, MNase-seq |
| GSM6424696 |
BRC patient P3, tumour breast tissue, MNase-assisted H3 ChIP-seq |
| GSM6424697 |
BRC patient P3, tumour breast tissue, MNase-seq |
| GSM6424698 |
BRC patient P4, normal breast tissue, MNase-assisted H3 ChIP-seq |
| GSM6424699 |
BRC patient P4, normal breast tissue, MNase-seq |
| GSM6424700 |
BRC patient P4, tumour breast tissue, MNase-assisted H3 ChIP-seq |
| GSM6424701 |
BRC patient P4, tumour breast tissue, MNase-seq |
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| Relations |
| BioProject |
PRJNA865250 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE210250_RAW.tar |
133.9 Gb |
(http)(custom) |
TAR (of BED, BW) |
| Raw data not provided for this record |
| Processed data provided as supplementary file |
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