Nucleosome reorganisation in breast cancer tissues.

Autor: Jacob DR; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK., Guiblet WM; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Mamayusupova H; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK., Shtumpf M; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK., Ciuta I; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK., Ruje L; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK., Gretton S; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK.; School of Engineering, Arts, Science and Technology, University of Suffolk, James Hehir Building, University Avenue, Ipswich, Suffolk, IP3 0FS, UK., Bikova M; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK., Correa C; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK., Dellow E; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK., Agrawal SP; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK., Shafiei N; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK., Drobysevskaja A; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK., Armstrong CM; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK., Lam JDG; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK., Vainshtein Y; Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB, Nobelstraße 12, 70569, Stuttgart, Germany., Clarkson CT; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK.; University College London, Gower St, Bloomsbury, London, WC1E 6BT, UK., Thorn GJ; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK.; Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK., Sohn K; Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB, Nobelstraße 12, 70569, Stuttgart, Germany., Pradeepa MM; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK.; Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, UK., Chandrasekharan S; Colchester General Hospital, East Suffolk and North Essex NHS Foundation Trust, Turner Road, Colchester, CO4 5JL, UK., Brooke GN; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK., Klenova E; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK., Zhurkin VB; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. zhurkin@nih.gov., Teif VB; School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK. vteif@essex.ac.uk.
Jazyk: angličtina
Zdroj: Clinical epigenetics [Clin Epigenetics] 2024 Apr 01; Vol. 16 (1), pp. 50. Date of Electronic Publication: 2024 Apr 01.
DOI: 10.1186/s13148-024-01656-4
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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