NAD Metabolism Drives CTCF-Cohesin Chromatin Regulation in EBV-Transformed B-Cells

Abstract

Chromatin architecture regulates gene expression, and it is maintained by architectural proteins such as CTCF and the cohesin complex. In Epstein Barr virus infected cells, viral chromatin organization is stabilized through the interaction between PARP1 and CTCF, ensuring maintenance of latent gene expression. EBV B cells exhibit elevated PARP1 activity, which imposes a substantial metabolic burden due to NAD consumption by PARP1 itself. We demonstrate that efficient EBV infection and B-cell transformation rely on the NAD salvage pathway to sustain PARP1 activity and CTCF and cohesin chromatin folding. Pharmacologic inhibition of the rate-limiting enzyme NAMPT with FK866 phenocopies the chromatin architectural disruption induced by PARP1 and changes in NAD levels affects CTCF/cohesin chromatin architectural remodeling and loop extrusion. Moreover, NAMPT inhibition reduces tumor burden in EBV xenograft models. These findings identify a critical metabolic dependency linking NAD homeostasis to CTCF-cohesin mediated chromatin architecture and reveal a therapeutic vulnerability in EBV-associated malignancies.

Intracellular complement Factor B couples inflammatory sensing to metabolism, chromatin regulation and maladaptive tissue repair
T. Freiwald, D. Chauss, M. Tajmul +22
bioRxiv4 Oct 2026PreprintCC0Full textImmunologybioRxiv
X-inactivation escapee domains are CTCF-cohesin independent chromatin compartments
A. Hauth, A. Loda, N. Bykov +11
bioRxiv31 Aug 2026PreprintCC BYFull textGenetics & genomicsbioRxiv
KAT3 Shuttling Between Neuronal Identity and Activity-Dependent Plasticity Programs Drives Large-Scale Chromatin Remodeling
S. Ninerola, B. del Blanco, M. Cangonja +6
bioRxiv28 Aug 2026PreprintAll rights reservedFull textNeurosciencebioRxiv
Systemic integration of chromatin and metabolism in stress memory: insights from grafted citrus
Abelmon da Silva Gesteira, Monique Ayala Araújo da Silva, Mauricio Antonio Coelho Filho
Annals of Botany16 Jul 2026Peer-reviewedPublisher termsFull textPlant biologyPMC
TIME FOR COFFEE coordinates phase separation and chromatin regulation for salt tolerance
Wenwen Tian, Xinheng Lyu, Grace R. Qian +1
Science advances16 Oct 2026Peer-reviewedCC BY-NCFull textPlant biologyEurope PMCCrossref

Cite

BibTeX RIS

BibTeX

@misc{maestri2026metabolism,
  title = {{NAD Metabolism Drives CTCF-Cohesin Chromatin Regulation in EBV-Transformed B-Cells}},
  author = {D. Maestri and R. Sklutuis and L. B. Caruso and S. Preston-Alp and M. Gatto and S. S. Soldan and P. Park and L. Melick and L. Corveleyn and S. Sidoli and A. Kossenkov and A. R. Goldman and W. Zhang and H.-Y. Tang and G. Napoletani and Y. Liao and P. M. Lieberman and B. E. Gewurz and I. Tempera},
  howpublished = {bioRxiv},
  year = {2026},
  month = nov,
  doi = {10.64898/2026.11.01.763250},
  url = {https://www.biorxiv.org/content/10.64898/2026.11.01.763250v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - NAD Metabolism Drives CTCF-Cohesin Chromatin Regulation in EBV-Transformed B-Cells
AU  - D. Maestri
AU  - R. Sklutuis
AU  - L. B. Caruso
AU  - S. Preston-Alp
AU  - M. Gatto
AU  - S. S. Soldan
AU  - P. Park
AU  - L. Melick
AU  - L. Corveleyn
AU  - S. Sidoli
AU  - A. Kossenkov
AU  - A. R. Goldman
AU  - W. Zhang
AU  - H.-Y. Tang
AU  - G. Napoletani
AU  - Y. Liao
AU  - P. M. Lieberman
AU  - B. E. Gewurz
AU  - I. Tempera
PY  - 2026
DA  - 2026/11/01
PB  - bioRxiv
DO  - 10.64898/2026.11.01.763250
UR  - https://www.biorxiv.org/content/10.64898/2026.11.01.763250v1
AB  - Chromatin architecture regulates gene expression, and it is maintained by architectural proteins such as CTCF and the cohesin complex. In Epstein Barr virus infected cells, viral chromatin organization is stabilized through the interaction between PARP1 and CTCF, ensuring maintenance of latent gene expression. EBV B cells exhibit elevated PARP1 activity, which imposes a substantial metabolic burden due to NAD consumption by PARP1 itself. We demonstrate that efficient EBV infection and B-cell transformation rely on the NAD salvage pathway to sustain PARP1 activity and CTCF and cohesin chromatin folding. Pharmacologic inhibition of the rate-limiting enzyme NAMPT with FK866 phenocopies the chromatin architectural disruption induced by PARP1 and changes in NAD levels affects CTCF/cohesin chromatin architectural remodeling and loop extrusion. Moreover, NAMPT inhibition reduces tumor burden in EBV xenograft models. These findings identify a critical metabolic dependency linking NAD homeostasis to CTCF-cohesin mediated chromatin architecture and reveal a therapeutic vulnerability in EBV-associated malignancies.
ER  -

Abstract

Related

Cite