title: Inhibition of H3K27me3-specific histone demethylases JMJD3 and UTX blocks reactivation of herpes simplex virus 1 in trigeminal ganglion neurons.
abstract: Herpes simplex virus 1 (HSV-1) genomes are associated with the repressive heterochromatic marks H3K9me2/me3 and H3K27me3 during latency. Previous studies have demonstrated that inhibitors of H3K9me2/me3 histone demethylases reduce the ability of HSV-1 to reactivate from latency. Here we demonstrate that GSK-J4, a specific inhibitor of the H3K27me3 histone demethylases UTX and JMJD3, inhibits HSV-1 reactivation from sensory neurons in vitro. These results indicate that removal of the H3K27me3 mark plays a key role in HSV-1 reactivation.
authors.affiliation: Department of Molecular Genetics & Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: Harald G P
authors.initials: HG
authors.lastname: Messer
authors.affiliation: Department of Molecular Genetics & Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Jacobs
authors.affiliation: Department of Molecular Genetics & Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: Adit
authors.initials: A
authors.lastname: Dhummakupt
authors.affiliation: Department of Molecular Genetics & Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA dbloom@ufl.edu.
authors.forename: David C
authors.initials: DC
authors.lastname: Bloom
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006561:Herpes Simplex / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D056466:Histone Demethylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D009474:Neurons / Q000201:enzymology / Q000378:metabolism* / Q000821:virology; D012668:Trigeminal Ganglion / Q000201:enzymology / Q000378:metabolism* / Q000821:virology; D014775:Virus Activation / Q000187:drug effects; D017735:Virus Latency / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C111778:Utx protein, mouse; C523761:Kdm6b protein, mouse