EBV infection is associated with histone bivalent switch modifications in squamous epithelial cells

Area of Science:

• Epigenetics
• Molecular Biology
• Oncology

Background:

• Epstein-Barr virus (EBV) is linked to tumorigenesis through poorly understood signaling pathway regulation.
• Histone modifications are key regulators of gene expression in EBV-driven cancers.

Purpose of the Study:

• To investigate the role of aberrant histone modifications in EBV-infected nasopharyngeal epithelial (NPE) cells.
• To elucidate the mechanisms of DNA damage repair gene regulation by EBV.

Main Methods:

• Analysis of histone marks (H3K4me3, H3K27me3) at DNA damage repair gene promoters in EBV-infected NPE cells.
• Quantification of MLH1 expression and assessment of cisplatin sensitivity.
• In vitro comet and apurinic/apyrimidinic site assays to evaluate DNA repair responsiveness.

Main Results:

• EBV infection induced aberrant histone bivalent switches, reducing H3K4me3 and increasing H3K27me3 at DNA repair gene promoters.
• MLH1, involved in mismatch repair, was downregulated in EBV-infected cells via histone modification, independent of promoter hypermethylation.
• EBV-infected cells exhibited reduced DNA damage repair capacity and altered cisplatin sensitivity.

Conclusions:

• EBV-associated aberrant histone bivalent switches suppress DNA damage repair genes in a methylation-independent manner.
• These epigenetic alterations are crucial in EBV-driven tumorigenesis and may influence therapeutic responses.