Nucleosome repositioning in chronic lymphocytic leukemia
© 2023 Piroeva et al.; Published by Cold Spring Harbor Laboratory Press..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
|---|---|
| Enthalten in: |
Genome research - 33(2023), 10 vom: 27. Okt., Seite 1649-1661 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Piroeva, Kristan V [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Chromatin |
|---|
| Anmerkungen: |
Date Completed 10.11.2023 Date Revised 05.12.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1101/gr.277298.122 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM361970064 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM361970064 | ||
| 003 | DE-627 | ||
| 005 | 20231226090250.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/gr.277298.122 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1206.xml |
| 035 | |a (DE-627)NLM361970064 | ||
| 035 | |a (NLM)37699659 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Piroeva, Kristan V |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Nucleosome repositioning in chronic lymphocytic leukemia |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 10.11.2023 | ||
| 500 | |a Date Revised 05.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 Piroeva et al.; Published by Cold Spring Harbor Laboratory Press. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Nucleosomes |2 NLM | |
| 650 | 7 | |a Chromatin |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 700 | 1 | |a McDonald, Charlotte |e verfasserin |4 aut | |
| 700 | 1 | |a Xanthopoulos, Charalampos |e verfasserin |4 aut | |
| 700 | 1 | |a Fox, Chelsea |e verfasserin |4 aut | |
| 700 | 1 | |a Clarkson, Christopher T |e verfasserin |4 aut | |
| 700 | 1 | |a Mallm, Jan-Philipp |e verfasserin |4 aut | |
| 700 | 1 | |a Vainshtein, Yevhen |e verfasserin |4 aut | |
| 700 | 1 | |a Ruje, Luminita |e verfasserin |4 aut | |
| 700 | 1 | |a Klett, Lara C |e verfasserin |4 aut | |
| 700 | 1 | |a Stilgenbauer, Stephan |e verfasserin |4 aut | |
| 700 | 1 | |a Mertens, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Kostareli, Efterpi |e verfasserin |4 aut | |
| 700 | 1 | |a Rippe, Karsten |e verfasserin |4 aut | |
| 700 | 1 | |a Teif, Vladimir B |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Genome research |d 1996 |g 33(2023), 10 vom: 27. Okt., Seite 1649-1661 |w (DE-627)NLM085678031 |x 1549-5469 |7 nnns |
| 773 | 1 | 8 | |g volume:33 |g year:2023 |g number:10 |g day:27 |g month:10 |g pages:1649-1661 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/gr.277298.122 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 33 |j 2023 |e 10 |b 27 |c 10 |h 1649-1661 | ||