Histone H3 Lysine 4 Methylation Marks Postreplicative Human Cytomegalovirus Chromatin

Abstract

<jats:p>In the nuclei of permissive cells, human cytomegalovirus genomes form nucleosomal structures initially resembling heterochromatin but gradually switching to a euchromatin-like state. This switch is characterized by a decrease in histone H3 K9 methylation and a marked increase in H3 tail acetylation and H3 K4 methylation across the viral genome. We used ganciclovir and a mutant virus encoding a reversibly destabilized DNA polymerase to examine the impact of DNA replication on histone modification dynamics at the viral chromatin. The changes in H3 tail acetylation and H3 K9 methylation proceeded in a DNA replication-independent fashion. In contrast, the increase in H3 K4 methylation proved to depend widely on viral DNA synthesis. Consistently, labeling of nascent DNA using “click chemistry” revealed preferential incorporation of methylated H3 K4 into viral (but not cellular) chromatin during or following DNA replication. This study demonstrates largely selective epigenetic tagging of postreplicative human cytomegalovirus chromatin.</jats:p>

Human Cytomegalovirus Major Immediate Early 1 Protein Targets Host Chromosomes by Docking to the Acidic Pocket on the Nucleosome Surface

“…Our prior work has demonstrated that nucleosomes are not confined to cellular chromatin but also form on hCMV nuclear DNA (87)(88)(89). We have also recently shown that global nucleosome occupancy and dynamics across hCMV genomes are largely controlled by IE1-dependent mechanisms (88).…”

Quantitative Proteomic Discovery of Dynamic Epigenome Changes that Control Human Cytomegalovirus (HCMV) Infection

“…Activating histone H3K9 and H3K14 acetylations are found at IE promoters as early as 3-6 h postinfection (hpi), prior to the acetylation at E or L promoters (4). Methylated H3K4, another activating mark, is incorporated into viral chromatin following its replication (5). Importantly, this study demonstrated selective epigenetic tagging of HCMV versus cellular chromatin.…”

Myeloblastic Cell Lines Mimic Some but Not All Aspects of Human Cytomegalovirus Experimental Latency Defined in Primary CD34+Cell Populations

“…Following reactivation, when IE1 is expressed, histones associated with the MIEP are acetylated, resembling transcriptionally active euchromatin (15,16). This mechanistically parallels the onset of lytic infection where, prior to IE gene expression, viral genomes show heterochromatic features, whereas later, when IE genes are being expressed, they are euchromatic (21)(22)(23).…”