Nucleosome repositioning in chronic lymphocytic leukemia

• Verfasst von: Piroeva, Kristan V. [VerfasserIn]
• Verfasst von: McDonald, Charlotte [VerfasserIn]
• Verfasst von: Xanthopoulos, Charalampos [VerfasserIn]
• Verfasst von: Fox, Chelsea [VerfasserIn]
• Verfasst von: Clarkson, Christopher T. [VerfasserIn]
• Verfasst von: Mallm, Jan-Philipp [VerfasserIn]
• Verfasst von: Vainshtein, Yevhen [VerfasserIn]
• Verfasst von: Ruje, Luminita [VerfasserIn]
• Verfasst von: Klett, Lara C. [VerfasserIn]
• Verfasst von: Stilgenbauer, Stephan [VerfasserIn]
• Verfasst von: Mertens, Daniel [VerfasserIn]
• Verfasst von: Kostareli, Efterpi [VerfasserIn]
• Verfasst von: Rippe, Karsten [VerfasserIn]
• Verfasst von: Teif, Vladimir [VerfasserIn]
• Titel: Nucleosome repositioning in chronic lymphocytic leukemia
• Verf.angabe: Kristan V. Piroeva, Charlotte McDonald, Charalampos Xanthopoulos, Chelsea Fox, Christopher T. Clarkson, Jan-Philipp Mallm, Yevhen Vainshtein, Luminita Ruje, Lara C. Klett, Stephan Stilgenbauer, Daniel Mertens, Efterpi Kostareli, Karsten Rippe and Vladimir B. Teif
• E-Jahr: 2023
• Jahr: December 2023
• Umfang: 13 S.
• Illustrationen: Illustrationen
• Fussnoten: Online verfügbar: 12. September 2023 ; Gesehen am 07.02.2024
• Titel Quelle: Enthalten in: Genome research
• Ort Quelle: Stanford, Calif. : HighWire Press, 1991
• Jahr Quelle: 2023
• Band/Heft Quelle: 33(2023), 10, Seite 1649-1661
• ISSN Quelle: 1549-5469
• DOI: doi:10.1101/gr.277298.122
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1880216744

Abstract

The location of nucleosomes in the human genome determines the primary chromatin structure and regulates access to regulatory regions. However, genome-wide information on deregulated nucleosome occupancy and its implications in primary cancer cells is scarce. Here, we conducted a genome-wide comparison of high-resolution nucleosome maps in peripheral blood B cells from patients with chronic lymphocytic leukemia (CLL) and healthy individuals at single-base-pair resolution. Our investigation uncovered significant changes of nucleosome positioning in CLL. Globally, the spacing between nucleosomes—the nucleosome repeat length (NRL)—is shortened in CLL. This effect is stronger in the more aggressive IGHV-unmutated CLL subtype than in the IGHV-mutated CLL subtype. Changes in nucleosome occupancy at specific sites are linked to active chromatin remodeling and reduced DNA methylation. Nucleosomes lost or gained in CLL marks differential binding of 3D chromatin organizers such as CTCF as well as immune response-related transcription factors and delineated mechanisms of epigenetic deregulation. The principal component analysis of nucleosome occupancy in cancer-specific regions allowed the classification of samples between cancer subtypes and normal controls. Furthermore, patients could be better assigned to CLL subtypes according to differential nucleosome occupancy than based on DNA methylation or gene expression. Thus, nucleosome positioning constitutes a novel readout to dissect molecular mechanisms of disease progression and to stratify patients. Furthermore, we anticipate that the global nucleosome repositioning detected in our study, such as changes in the NRL, can be exploited for liquid biopsy applications based on cell-free DNA to stratify patients and monitor disease progression.