biostudies-literatureUnknown99(12)Arbuckle JHNational Institute of Allergy and Infectious DiseasesEpigenetic modulation of herpes simplex virus (HSV) immediate early (IE) genes is a critical parameter governing lytic infection, latency, and viral reactivation. Multiple factors, including epigenetic complexes associated with the cellular transcriptional coactivator HCF-1, modulate the state of HSV-1 chromatin. Although some aspects of HSV-1 chromatin biology have been elucidated, many epigenetic factors controlling HSV-1 chromatin accessibility and transcriptional regulation remain unknown. To identify novel epigenetic regulators of the initial stage of HSV-1 infection, an epigenetic chemical probe library was screened for molecules that impacted viral IE gene expression. This screen identified several epigenetic inhibitors that modulated IE expression. Notably, UNC0379, an inhibitor ofJournal of virologye0129325https://www.ebi.ac.uk/biostudies/studies/S-EPMC12724366biostudies-literatureThe H4K20-mono-methyltransferase SETD8 promotes global accessibility of infecting herpes simplex virus genomes.PMC12724366Vogel JLMcBride AAMarkowitz TEYanez AAKristie TMArbuckle JHBaksh SSfalseThe H4K20-mono-methyltransferase SETD8 promotes global accessibility of infecting herpes simplex virus genomes.Epigenetic modulation of herpes simplex virus (HSV) immediate early (IE) genes is a critical parameter governing lytic infection, latency, and viral reactivation. Multiple factors, including epigenetic complexes associated with the cellular transcriptional coactivator HCF-1, modulate the state of HSV-1 chromatin. Although some aspects of HSV-1 chromatin biology have been elucidated, many epigenetic factors controlling HSV-1 chromatin accessibility and transcriptional regulation remain unknown. To identify novel epigenetic regulators of the initial stage of HSV-1 infection, an epigenetic chemical probe library was screened for molecules that impacted viral IE gene expression. This screen identified several epigenetic inhibitors that modulated IE expression. Notably, UNC0379, an inhibitor of2025-01-01T00:00:00Z2025 Dec2026-06-08T05:17:31.065Z2026-06-08T03:09:01.277ZS-EPMC127243664125871210.1128/jvi.01293-25