Alteration of Histone H3 Lysine 4 Trimethylation on Putative Lytic Gene Promoters by Human Set1 Complex during Reactivation of Kaposi's Sarcoma-Associated Herpesvirus

Abstract

Objective: Histone H3 lysine 4 is trimethylated by the human Set1 complex, which regulates the activation of gene expression. The aim of this study was to identify whether the levels of histone H3 lysine 4 trimethylation (H3K4me3) and the recruitment of human Set1 complex at the promoter regions of lytic genes quantitatively change during reactivation from latent to lytic infection of Kaposi's sarcoma-association herpesvirus (KSHV). Methods: During KSHV reactivation, global changes of H3K4 methylation in KSHV-infected cells were analyzed by Western blot. The relative levels of association between proteins and promoter regions were determined by chromatin immunoprecipitation assay and quantitative real-time PCR using specific antibodies and primer sets. Results: Our results showed that KSHV reactivation does not alter the overall cellular levels of H3K4 methylation. We observed that the switch from latency to lytic cycle leads to upregulation of H3K4me3 at the active lytic genes. We also found that the recruitment of RNA pol II and subunits of human Set1 complex were enriched at the same regions in response to KSHV reactivation. Conclusion: These results demonstrate that the increase of H3K4me3 by human Set1 complex is involved in activation of lytic genes during the lytic infection of KSHV. Copyright (c) 2013 S. Karger AG, Basel