Reorganization of the host epigenome by a viral oncogene

Adenovirus small e1a causes ~70% reduction in cellular levels of histone H3 lysine 18 acetylation (H3K18ac). It is unclear, however, where this dramatic reduction occurs genome-wide. ChIP-seq revealed that e1a erases 95% of H3K18ac peaks in normal fibroblasts and replaces them with one-third as many at new genomic locations. H3K18ac at promoters and intergenic regions of genes with fibroblast-related functions are relocalized after infection to promoters of highly-induced genes that regulate cell cycling and to new putative enhancers. Strikingly, a significant fraction of the post-infection H3K18ac peaks occurs precisely at regions bound by RB1 in uninfected cells, but not by p107 or p130 without RB1. In contrast, over half of H3K9ac peaks are similarly distributed before and after infection, independently of RB1. The strategic redistribution of H3K18ac by e1a highlights the importance of this modification for transcriptional activation and cellular transformation. Examination of two histone acetylations and RB family members binding. mRNA-Seq RPKM file linked as supplementary file on Series record.