title: CTCF occupation of the herpes simplex virus 1 genome is disrupted at early times postreactivation in a transcription-dependent manner.
abstract: In herpes simplex virus 1 (HSV-1), binding clusters enriched in CTCF during latency have been previously identified. We hypothesized that CTCF binding to CTCF clusters in HSV-1 would be disrupted in a reactivation event. To investigate, CTCF occupation of three CTCF binding clusters in HSV-1 was analyzed following sodium butyrate (NaB)- and explant-induced reactivation in the mouse. Our data show that the CTCF domains positioned within the HSV-1 genome, specifically around the latency-associated transcript (LAT) and ICP0 and ICP4 regions of the genome, lose CTCF occupancy following the application of reactivation stimuli in wild-type virus. We also found that CTCF binding clusters upstream of the ICP0 and ICP4 promoters both function as classical insulators capable of acting as enhancer blockers of the LAT enhancer. Finally, our results suggest that CTCF occupation of domains in HSV-1 may be differentially regulated both during latency and at early times following reactivation by the presence of lytic transcripts and further implicate epigenetic regulation of HSV-1 as a critical component of the latency-reactivation transition.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Monica K
authors.initials: MK
authors.lastname: Ertel
authors.forename: Amy L
authors.initials: AL
authors.lastname: Cammarata
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Hron
authors.forename: Donna M
authors.initials: DM
authors.lastname: Neumann
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000076246:CCCTC-Binding Factor; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics* / Q000502:physiology; D005260:Female; D016679:Genome, Viral / Q000235:genetics*; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014775:Virus Activation / Q000235:genetics* / Q000502:physiology; D017735:Virus Latency / Q000235:genetics*
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; C000619698:Ctcf protein, mouse; D017931:DNA Primers; D012097:Repressor Proteins