The three-dimensional structure of Epstein-Barr virus genome varies by latency type and is regulated by PARP1 enzymatic activity.
B-Lymphocytes
/ pathology
CCCTC-Binding Factor
/ metabolism
Cell Cycle Proteins
/ genetics
Chromatin
/ chemistry
Chromosomal Proteins, Non-Histone
/ genetics
Chromosome Mapping
/ methods
Epstein-Barr Virus Infections
/ virology
Gene Expression Regulation
Genome, Viral
Herpesvirus 4, Human
/ drug effects
Host-Pathogen Interactions
Humans
Models, Molecular
Phthalazines
/ pharmacology
Piperazines
/ pharmacology
Plasmids
/ metabolism
Poly (ADP-Ribose) Polymerase-1
/ genetics
Protein Binding
Signal Transduction
Transcription, Genetic
Virus Latency
/ genetics
Cohesins
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 01 2022
17 01 2022
Historique:
received:
23
10
2020
accepted:
21
12
2021
entrez:
18
1
2022
pubmed:
19
1
2022
medline:
9
2
2022
Statut:
epublish
Résumé
Epstein-Barr virus (EBV) persists in human B-cells by maintaining its chromatinized episomes within the nucleus. We have previously shown that cellular factor Poly [ADP-ribose] polymerase 1 (PARP1) binds the EBV genome, stabilizes CTCF binding at specific loci, and that PARP1 enzymatic activity correlates with maintaining a transcriptionally active latency program. To better understand PARP1's role in regulating EBV latency, here we functionally characterize the effect of PARP enzymatic inhibition on episomal structure through in situ HiC mapping, generating a complete 3D structure of the EBV genome. We also map intragenomic contact changes after PARP inhibition to global binding of chromatin looping factors CTCF and cohesin across the EBV genome. We find that PARP inhibition leads to fewer total unique intragenomic interactions within the EBV episome, yet new chromatin loops distinct from the untreated episome are also formed. This study also illustrates that PARP inhibition alters gene expression at the regions where chromatin looping is most effected. We observe that PARP1 inhibition does not alter cohesin binding sites but does increase its frequency of binding at those sites. Taken together, these findings demonstrate that PARP has an essential role in regulating global EBV chromatin structure and latent gene expression.
Identifiants
pubmed: 35039491
doi: 10.1038/s41467-021-27894-1
pii: 10.1038/s41467-021-27894-1
pmc: PMC8764100
doi:
Substances chimiques
CCCTC-Binding Factor
0
CTCF protein, human
0
Cell Cycle Proteins
0
Chromatin
0
Chromosomal Proteins, Non-Histone
0
Phthalazines
0
Piperazines
0
PARP1 protein, human
EC 2.4.2.30
Poly (ADP-Ribose) Polymerase-1
EC 2.4.2.30
olaparib
WOH1JD9AR8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
187Subventions
Organisme : NIAID NIH HHS
ID : R01 AI130209
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE017336
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA093606
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA010815
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA211199
Pays : United States
Informations de copyright
© 2022. The Author(s).
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