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- Title
Nucleosome DNA unwrapping does not affect prototype foamy virus integration efficiency or site selection.
- Authors
Mackler, Randi M.; Jones, Nathan D.; Gardner, Anne M.; Lopez Jr., Miguel A.; Howard, Cecil J.; Fishel, Richard; Yoder, Kristine E.
- Abstract
Eukaryotic DNA binding proteins must access genomic DNA that is packaged into chromatin in vivo. During a productive infection, retroviral integrases (IN) must similarly interact with chromatin to integrate the viral cDNA genome. Here we examine the role of nucleosome DNA unwrapping in the retroviral integrase search for a target site. These studies utilized PFV intasomes that are comprised of a tetramer of PFV IN with two oligomers mimicking the viral cDNA ends. Modified recombinant human histones were used to generate nucleosomes with increased unwrapping rates at different DNA regions. These modifications included the acetylmimetic H3(K56Q) and the chemically engineered H4(K77ac, K79ac). While transcription factors and DNA damage sensors may search nucleosome bound DNA during transient unwrapping, PFV intasome mediated integration appears to be unaffected by increased nucleosome unwrapping. These studies suggest PFV intasomes do not utilize nucleosome unwrapping to search nucleosome targets.
- Subjects
DNA-binding proteins; FOAMY viruses; DNA; ANTISENSE DNA; TRANSCRIPTION factors; VIRAL genomes
- Publication
PLoS ONE, 2019, Vol 14, Issue 3, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0212764