Adenovirus
Epigenetic Reprogramming by Adenovirus e1a
22/08/2008
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.
Science 22 August 2008: Vol. 321. no. 5892, pp. 1086 - 1088, DOI: 10.1126/science.1155546
Science 22 August 2008: Vol. 321. no. 5892, pp. 1086 - 1088, DOI: 10.1126/science.1155546
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