期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-27894-1
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资金
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R01AI130209]
- National Institute of Dental and Craniofacial Research of the National Institutes of Health [R01 DE017336]
This study demonstrates the essential role of PARP1 in regulating the chromatin structure and gene expression of EBV. PARP inhibition leads to decreased intragenomic interactions within the EBV episome, but also forms new chromatin loops. Additionally, PARP inhibition alters the binding of chromatin looping factor CTCF and gene expression.
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. Genome folding in the nucleus plays an important role in regulating gene expression. Here the authors show that 3D genome architecture also plays an important role for gene expression adaptability for the Epstein-Barr Virus (EBV), a virus that is associated with cancer. They also observe major changes in the fold of the EBV chromosome between silent and transcriptional active viral genomes.
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