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Reorganization of the host epigenome by a viral oncogene

    • 1Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA;
    • 2Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, California 90095, USA;
    • 3Division of Oral Biology and Medicine, School of Dentistry, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA;
    • 4UCLA Bioinformatics Interdepartmental Degree Program, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA;
    • 5Department of Molecular, Cellular, and Developmental Biology, University of California, Los Angeles, California 90095, USA;
    • 6Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA;
    • 7Molecular Biology Institute, University of California, Los Angeles, California 90095, USA;
    • 8Department of Pathology and Laboratory of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA
Published April 12, 2012. https://doi.org/10.1101/gr.132308.111
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cover of Genome Research Vol 36 Issue 7
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July 2026, Vol. 36, No. 7
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Abstract

Adenovirus small e1a oncoprotein 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-sequencing revealed that by 24 h after expression, e1a erases 95% of H3K18ac peaks in normal, contact-inhibited fibroblasts and replaces them with one-third as many at new genomic locations. The H3K18ac peaks at promoters and intergenic regions of genes with fibroblast-related functions are eliminated after infection, and new H3K18ac peaks are established at promoters of highly induced genes that regulate cell cycling and at new putative enhancers. Strikingly, the regions bound by the retinoblastoma family of proteins in contact-inhibited fibroblasts gain new peaks of H3K18ac in the e1a-expressing cells, including 55% of RB1-bound loci. 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 as well as functional differences between the RB-family member proteins.

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