Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 22 August 2008:
Vol. 321. no. 5892, pp. 1086 - 1088
DOI: 10.1126/science.1155546
Prev | Table of Contents | Next

Reports

Epigenetic Reprogramming by Adenovirus e1a

Roberto Ferrari,1 Matteo Pellegrini,2 Gregory A. Horwitz,3 Wei Xie,1 Arnold J. Berk,3,4 Siavash K. Kurdistani1,5,6*

Adenovirus e1a induces quiescent human cells to replicate. We found that e1a causes global relocalization of the RB (retinoblastoma) proteins (RB, p130, and p107) and p300/CBP histone acetyltransferases on promoters, the effect of which is to restrict the acetylation of histone 3 lysine-18 (H3K18ac) to a limited set of genes, thereby stimulating cell cycling and inhibiting antiviral responses and cellular differentiation. Soon after expression, e1a binds transiently to promoters of cell cycle and growth genes, causing enrichment of p300/CBP, PCAF (p300/CBP-associated factor), and H3K18ac; depletion of RB proteins; and transcriptional activation. e1a also associates transiently with promoters of antiviral genes, causing enrichment for RB, p130, and H4K16ac; increased nucleosome density; and transcriptional repression. At later times, e1a and p107 bind mainly to promoters of development and differentiation genes, repressing transcription. The temporal order of e1a binding requires its interactions with p300/CBP and RB proteins. Our data uncover a defined epigenetic reprogramming leading to cellular transformation.

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.

* To whom correspondence should be addressed. E-mail: skurdistani{at}mednet.ucla.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Transgenerational genetic effects on phenotypic variation and disease risk.
J. H. Nadeau (2009)
Hum. Mol. Genet. 18, R202-R210
   Abstract »    Full Text »    PDF »
Adenovirus E1A Inhibits SCFFbw7 Ubiquitin Ligase.
T. Isobe, T. Hattori, K. Kitagawa, C. Uchida, Y. Kotake, I. Kosugi, T. Oda, and M. Kitagawa (2009)
J. Biol. Chem. 284, 27766-27779
   Abstract »    Full Text »    PDF »
Structural basis for subversion of cellular control mechanisms by the adenoviral E1A oncoprotein.
J. C. Ferreon, M. A. Martinez-Yamout, H. J. Dyson, and P. E. Wright (2009)
PNAS 106, 13260-13265
   Abstract »    Full Text »    PDF »
Epigenetics in cancer: Targeting chromatin modifications.
L. Ellis, P. W. Atadja, and R. W. Johnstone (2009)
Mol. Cancer Ther. 8, 1409-1420
   Abstract »    Full Text »    PDF »
Adenovirus Transforming Protein E1A Induces c-Myc in Quiescent Cells by a Novel Mechanism.
R.-K. Kadeppagari, N. Sankar, and B. Thimmapaya (2009)
J. Virol. 83, 4810-4822
   Abstract »    Full Text »    PDF »
Global Histone Modifications in Breast Cancer Correlate with Tumor Phenotypes, Prognostic Factors, and Patient Outcome.
S. E. Elsheikh, A. R. Green, E. A. Rakha, D. G. Powe, R. A. Ahmed, H. M. Collins, D. Soria, J. M. Garibaldi, C. E. Paish, A. A. Ammar, et al. (2009)
Cancer Res. 69, 3802-3809
   Abstract »    Full Text »    PDF »
Global Levels of Histone Modifications Predict Prognosis in Different Cancers.
D. B. Seligson, S. Horvath, M. A. McBrian, V. Mah, H. Yu, S. Tze, Q. Wang, D. Chia, L. Goodglick, and S. K. Kurdistani (2009)
Am. J. Pathol. 174, 1619-1628
   Abstract »    Full Text »    PDF »
Adenovirus Small e1a Alters Global Patterns of Histone Modification.
G. A. Horwitz, K. Zhang, M. A. McBrian, M. Grunstein, S. K. Kurdistani, and A. J. Berk (2008)
Science 321, 1084-1085
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)