Adenovirus small e1a alters global patterns of histone modification

被引:168
作者
Horwitz, Gregory A. [1 ]
Zhang, Kangling [2 ]
McBrian, Matthew A. [3 ]
Grunstein, Michael [3 ]
Kurdistani, Siavash K. [3 ]
Berk, Arnold J. [1 ,4 ]
机构
[1] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA
[2] Loma Linda Univ, Mass Spectrometry Facil, Dept Biochem, Sch Med, Loma Linda, CA 92350 USA
[3] Univ Calif Los Angeles, Dept Biol Chem, David Geffen Sch Med, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA
关键词
D O I
10.1126/science.1155544
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1084 / 1085
页数:2
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