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Isolation of Viral Replication Compartment-enriched Sub-nuclear Fractions from Adenovirus-infected Normal Human Cells
Published on: November 12, 2015
Adenovirus small e1a alters global patterns of histone modification
Gregory A Horwitz1, Kangling Zhang, Matthew A McBrian
1Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
Science (New York, N.Y.)
|August 23, 2008
Summary
Adenovirus e1a protein links to cell cycle progression by reducing histone H3 lysine 18 acetylation (H3K18ac). This finding suggests a role for H3K18 hypoacetylation in cancer development.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Adenovirus e1a protein induces cell cycle progression by interacting with RB proteins and histone acetyltransferases p300/CBP.
- The precise mechanism by which e1a binding to p300/CBP facilitates cell cycle progression remains incompletely understood.
Purpose of the Study:
- To elucidate the role of the e1a interaction with p300 and CBP in promoting cell cycle passage.
- To investigate the impact of e1a on histone acetylation, specifically at histone H3 lysine 18 (H3K18).
Main Methods:
- Investigated the interaction between adenovirus e1a protein, RB family proteins, and histone acetyltransferases p300/CBP.
- Quantified global histone H3 lysine 18 acetylation (H3K18ac) levels.
- Utilized knockdown of CBP and p300 to assess their role in H3K18ac.
- Examined H3K18ac levels in cells expressing SV40 T antigen and in prostate carcinoma tissues.
Main Results:
- The e1a interaction with p300/CBP led to a threefold reduction in global H3K18ac.
- Knockdown of CBP and p300 specifically caused H3K18 hypoacetylation, confirming their role in H3K18 acetylation.
- SV40 T antigen also induced H3K18 hypoacetylation.
- Global H3K18 hypoacetylation was observed in prostate carcinomas associated with poor prognosis.
Conclusions:
- The adenovirus e1a protein promotes cell cycle progression, at least in part, by reducing H3K18 acetylation.
- Global H3K18 hypoacetylation is a potential mechanism linked to oncogenic transformation and may serve as a biomarker for aggressive cancers.
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