Chromatin reorganisation in Epstein-Barr virus-infected cells and its role in cancer development

- Key EBV transcription factors hijack host cell factors to reprogramme B cells.
- This is mostly directed through binding to host gene enhancers and super-enhancers.
- Binding can promote or disrupt enhancer-promoter contacts to turn genes on or off.
- EBV activation of upstream MYC enhancers may promote upstream MYC translocations.
- Enhancer hub disruption by EBV can initiate long term gene silencing.

The oncogenic Epstein-Barr virus (EBV) growth transforms B cells and drives lymphoma and carcinoma development. The virus encodes four key transcription factors (EBNA2, EBNA3A, EBNA3B and EBNA3C) that hijack host cell factors to bind gene control elements and reprogramme infected B cells. These viral factors predominantly target long-range enhancers to alter the expression of host cell genes that control B cell growth and survival and facilitate virus persistence. Enhancer and super-enhancer binding by these EBNAs results in large-scale reorganisation of three-dimensional enhancer-promoter architecture to drive the overexpression of oncogenes, the silencing of tumour suppressors and the modulation of transcription, cell-cycle progression, migration and adhesion.