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Science 22 August 2008:
Vol. 321. no. 5892, pp. 1086 - 1088
DOI: 10.1126/science.1155546
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Reports

Epigenetic Reprogramming by Adenovirus e1a

Roberto Ferrari1, Matteo Pellegrini2, Gregory A. Horwitz3, Wei Xie1, Arnold J. Berk3,4 and Siavash K. Kurdistani1,5,6*

1 Department of Biological Chemistry, University of California, Los Angeles, CA 90095, USA.
2 Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
3 Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
4 Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
5 Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA.
6 Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.


Figure 1 Fig. 1. Temporally ordered pattern of e1a binding reprograms host cell gene expression profile. (A) Time course of e1a genome-wide localization in IMR90 fibroblasts. Each row represents the promoter of a gene in 500-bp intervals from –5.5 to +2.5 kb of the transcription start site (TSS). Enrichment Z scores are indicated to the right of each cluster. (B) Relative gene expression changes of the three clusters at 6, 12, and 24 hours after e1a expression (note the scale). [View Larger Version of this Image (26K GIF file)]
 

Figure 2 Fig. 2. Redistribution of transcriptional co-regulators and epigenetic reprogramming by e1a. The genome-wide distributions of p300, H3K18ac, H3K9ac, H4K16ac, histone H3, RB, p130, and p107 in the three e1a-binding clusters at the indicated times after e1a expression are shown. [View Larger Version of this Image (106K GIF file)]
 

Figure 3 Fig. 3. Temporally ordered target gene selection and proper binding by e1a requires interactions with p300/CBP and the RB proteins. (A and C) Time course of R2Ge1a and {Delta}CR2e1a genome-wide localization in IMR90 fibroblasts in the three WTe1a-binding clusters (Fig. 1A). Also shown are the distribution and enrichment Z scores of H3K9ac and H3K18ac in R2Ge1a- or {Delta}CR2e1a-infected versus mock-infected cells. (B and D) Relative expression levels of the three clusters in each mutant 24 hours after e1a expression. [View Larger Version of this Image (89K GIF file)]
 

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