biostudies-literatureDunn LEMNIAID NIH HHSNational Institutes of HealthNIH HHS1169https://www.ebi.ac.uk/biostudies/studies/S-EPMC12474073biostudies-literatureUnknown17(9)Herpes simplex virus 1 (HSV-1) transcribes its genome using host RNA polymerase II (Pol II) in a temporally regulated cascade. We previously proposed a model of Transient Immediate Early gene Mediated Repression (TIEMR), in which early repression of immediate early (IE) genes is relieved to initiate the cascade. Given the rapid association of promyelocytic leukaemia nuclear body (PML-NB) components with incoming HSV-1 genomes, we sought to investigate their roles in TIEMR. siRNA knockdown revealed that depletion of ATRX, but not PML, significantly reduced nascent transcription from viral IE promoters at 1.5 hpi, while DAXX knockdown increased transcription. ChIP-Seq showed ATRX localizes to both transcriptionally active IE genes and restricted non-IE genes, suggesting diverse functions. NoVirusesATRX Promotes Transcription Initiation of HSV-1 Immediate Early Genes During Early Lytic Infection.PMC124740731R01AI141968-061R01 AI 141968-06R01 AI141968Clark MMBaines JDDunn LEMfalseATRX Promotes Transcription Initiation of HSV-1 Immediate Early Genes During Early Lytic Infection.Herpes simplex virus 1 (HSV-1) transcribes its genome using host RNA polymerase II (Pol II) in a temporally regulated cascade. We previously proposed a model of Transient Immediate Early gene Mediated Repression (TIEMR), in which early repression of immediate early (IE) genes is relieved to initiate the cascade. Given the rapid association of promyelocytic leukaemia nuclear body (PML-NB) components with incoming HSV-1 genomes, we sought to investigate their roles in TIEMR. siRNA knockdown revealed that depletion of ATRX, but not PML, significantly reduced nascent transcription from viral IE promoters at 1.5 hpi, while DAXX knockdown increased transcription. ChIP-Seq showed ATRX localizes to both transcriptionally active IE genes and restricted non-IE genes, suggesting diverse functions. No2025-01-01T00:00:00Z2025 Aug2026-07-05T03:16:53.701Z2026-07-05T03:12:21.492ZS-EPMC124740734101259710.3390/v17091169