Adenovirus Small e1a Alters Global Patterns of Histone Modification
Gregory A. Horwitz,1
Kangling Zhang,2
Matthew A. McBrian,3
Michael Grunstein,3
Siavash K. Kurdistani,3
Arnold J. Berk1,4*
Adenovirus small early region 1a (e1a) protein drives cells into S phase by binding RB family proteins and the closely related histone acetyl transferases p300 and CBP. The interaction with RB proteins displaces them from DNA-bound E2F transcription factors, reversing their repression of cell cycle genes. However, it has been unclear how the e1a interaction with p300 and CBP promotes passage through the cell cycle. We show that this interaction causes a threefold reduction in total cellular histone H3 lysine 18 acetylation (H3K18ac). CBP and p300 are required for acetylation at this site because their knockdown causes specific hypoacetylation at H3K18. SV40 T antigen also induces H3K18 hypoacetylation. Because global hypoacetylation at this site is observed in prostate carcinomas with poor prognosis, this suggests that processes resulting in global H3K18 hypoacetylation may be linked to oncogenic transformation.
1 Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
2 Mass Spectrometry Facility, Department of Biochemistry, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
3 Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
4 Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
* To whom correspondence should be addressed. E-mail: berk{at}mbi.ucla.edu
