Epigenetic reprogramming by adenovirus e1a

被引：175

作者：

Ferrari, Roberto ^{[1
]}

Pellegrini, Matteo ^{[2
]}

Horwitz, Gregory A. ^{[3
]}

Xie, Wei ^{[1
]}

Berk, Arnold J. ^{[3
,4
]}

Kurdistani, Siavash K. ^{[1
,5
,6
]}

机构：

[1] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, David Geffen Sch Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA

来源：

SCIENCE | 2008年 / 321卷 / 5892期

关键词：

D O I：

10.1126/science.1155546

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 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.

引用

页码：1086 / 1088

页数：3

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