The three-dimensional structure of Epstein-Barr virus genome varies by latency type and is regulated by PARP1 enzymatic activity, 2022 Sarah M. Morgan

Abstract
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.

https://www.nature.com/articles/s41467-021-27894-1

The drug olaparib (Lynparza), which is approved for the treatment of people with ovarian cancer, targets PARP1. Scientists found that such a PARP inhibitor can also reprogram EBV and how its genes are expressed.

New research also shows that olaparib may be useful for the treatment of cancers linked to EBV.

“Our paper shows that there is another role of PARP1 in the chromatin folding,” Tempera said, “so this suggests that maybe we can expand the way in which we can use this drug not only to interfere with DNA damage, but we also might interfere with DNA folding and gene expression, which is something that we are testing now in the lab.”

The researchers are also looking to explore what role, if any, PARP1 plays in the human genome’s folding.

https://www.gilmorehealth.com/wista...d-be-targeted-in-fighting-epstein-barr-virus/