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Journal of Virology, August 2000, p. 7230-7237, Vol. 74, No. 16
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
The Human Cytomegalovirus 86-Kilodalton Major Immediate-Early
Protein Interacts Physically and Functionally with Histone
Acetyltransferase P/CAF
L. A.
Bryant,1
P.
Mixon,1
M.
Davidson,1
A. J.
Bannister,2
T.
Kouzarides,2 and
J. H.
Sinclair1,*
Department of Medicine, Addenbrooke's
Hospital,1 and Wellcome/CRC Institute
and Department of Pathology,2 University of
Cambridge, Cambridge CB2 2QQ, United Kingdom
Received 4 February 2000/Accepted 17 May 2000
The major immediate-early proteins of human cytomegalovirus (HCMV)
play a pivotal role in controlling viral and cellular gene expression
during productive infection. As well as negatively autoregulating its
own promoter, the HCMV 86-kDa major immediate early protein (IE86)
activates viral early gene expression and is known to be a promiscuous
transcriptional regulator of cellular genes. IE86 appears to act as a
multimodal transcription factor. It is able to bind directly to target
promoters to activate transcription but is also able to bridge between
upstream binding factors such as CREB/ATF and the basal transcription
complex as well as interacting directly with general transcription
factors such as TATA-binding protein and TFIIB. We now show that IE86
is also able to interact directly with histone acetyltransferases
during infection. At least one of these factors is the histone
acetyltransferase CBP-associated factor (P/CAF). Furthermore, we show
that this interaction results in synergistic transactivation by IE86 of
IE86-responsive promoters. Recruitment of such chromatin-remodeling
factors to target promoters by IE86 may help explain the ability of
this viral protein to act as a promiscuous transactivator of cellular genes.
*
Corresponding author. Mailing address: Department of
Medicine, University of Cambridge, Level 5, Addenbrooke's Hospital,
Hills Road, Cambridge CB2 2QQ, United Kingdom. Phone: 01223 336850. Fax: 01223 336846. E-mail:
js{at}mole.bio.cam.ac.uk.
Journal of Virology, August 2000, p. 7230-7237, Vol. 74, No. 16
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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