SV40 virion formation functions as a novel epigenetic switch controlling early and late transcription

Abstract

Simian Virus 40 (SV40) is a small double‐strand DNA virus, which exists in the form of chromatin throughout its lifecycle. Because of its chromatin structure, the virus is expected to undergo the typical forms of epigenetic regulation, including differential nucleosome location and histone modifications. In order to characterize the epigenetic changes occurring during the formation of virions from late‐stage SV40 minichromosomes (encapsidation), we have compared the location of nucleosomes containing acetylated or methylated lysines from the histone tails of H3 and H4 present in the chromatin from late‐stage minichromosomes, encapsidation intermediates, and disrupted virions. In late‐stage minichromosomes, we found that nucleosomes carrying histone modifications were primarily found in the SV40 regulatory region within the enhancer and at the early and late transcription start sites. Significantly, the nucleosome containing modified histones within the enhancer would be expected to repress early transcription by overlying regulatory sequences in the SP1 and enhancer regions required for early transcription while still allowing for late transcription. In contrast, in chromatin from virions the nucleosome found in the enhancer has been shifted approximately 70 base‐pairs toward the late region uncovering the regulatory sequences necessary for early transcription and likely repressing late transcription. This encapsidation‐dependent epigenetic switch was associated with the final stages of virion formation.Support or Funding InformationThis work was funded by grants from the National Institutes of Health, AI094441 (to B.M.) and GM098328 (to L.B.) and P20 GM113123 (to Epigenetics Core)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.