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Cell Host Microbe. 2014 Nov 12;16(5):663-76. doi: 10.1016/j.chom.2014.10.004. Epub 2014 Nov 12.

Adenovirus small E1A employs the lysine acetylases p300/CBP and tumor suppressor Rb to repress select host genes and promote productive virus infection.

Author information

1
Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
2
Molecular Biology Institute, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA; Department of Microbiology, Immunology and Molecular Genetics, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
3
Molecular Biology Institute, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
4
Department of Microbiology, Immunology and Molecular Genetics, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
5
Department of Biological Chemistry, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
6
Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA; Molecular Biology Institute, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA; Department of Molecular, Cellular, and Developmental Biology, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
7
Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA; Molecular Biology Institute, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA; Department of Biological Chemistry, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA; Department of Pathology and Laboratory of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
8
Molecular Biology Institute, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA; Department of Microbiology, Immunology and Molecular Genetics, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA. Electronic address: berk@mbi.ucla.edu.

Abstract

Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with the host lysine acetylases p300/CBP and the tumor suppressor RB. How these interactions influence cellular gene expression remains unclear. We find that e1a displaces RBs from E2F transcription factors and promotes p300 acetylation of RB1 K873/K874 to lock it into a repressing conformation that interacts with repressive chromatin-modifying enzymes. These repressing p300-e1a-RB1 complexes specifically interact with host genes that have unusually high p300 association within the gene body. The TGF-β, TNF-, and interleukin-signaling pathway components are enriched among such p300-targeted genes. The p300-e1a-RB1 complex condenses chromatin in a manner dependent on HDAC activity, p300 lysine acetylase activity, the p300 bromodomain, and RB K873/K874 and e1a K239 acetylation to repress host genes that would otherwise inhibit productive virus infection. Thus, adenovirus employs e1a to repress host genes that interfere with viral replication.

PMID:
25525796
PMCID:
PMC4418520
DOI:
10.1016/j.chom.2014.10.004
[Indexed for MEDLINE]
Free PMC Article

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