HDAC inhibitors stimulate viral transcription by multiple mechanisms.
BACKGROUND
The effects of histone deacetylase inhibitor (HDACi) treatment on SV40 transcription and replication were determined by monitoring the levels of early and late expression, the extent of replication, and the percentage of SV40 minichromosomes capable of transcription and replication following treatment with sodium butyrate (NaBu) and trichostatin A (TSA).


RESULTS
The HDACi treatment was found to maximally stimulate early transcription at early times and late transcription at late times through increased numbers of minichromosomes which carry RNA polymerase II (RNAPII) transcription complexes and increased occupancy of the transcribing minichromosomes by RNAPII. HDACi treatment also partially relieved the normal down-regulation of early transcription by T-antigen seen later in infection. The increased recruitment of transcribing minichromosomes at late times was correlated to a corresponding reduction in SV40 replication and the percentage of minichromosomes capable of replication.


CONCLUSIONS
These results suggest that histone deacetylation plays a critical role in the regulation of many aspects of an SV40 lytic infection.
Balakrishnan
Lata
L
Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, North Dakota, USA. lbalakrishnan@medicine.nodak.edu
Milavetz
Barry
B
D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D002460:Cell Line; D002875:Chromosomes / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000494:pharmacology*; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D013539:Simian virus 40 / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D014764:Viral Proteins; C012589:trichostatin A; D012319:RNA Polymerase II