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Molecular and Cellular Biology, March 1999, p. 1810-1820, Vol. 19, No. 3
0270-7306/99
The Histone Acetylase PCAF Is a Phorbol-Ester-Inducible
Coactivator of the IRF Family That Confers Enhanced
Interferon Responsiveness
Atsuko
Masumi,
I-Ming
Wang,
Bruno
Lefebvre,
Xing-Jiao
Yang,
Yoshihiro
Nakatani, and
Keiko
Ozato*
Laboratory of Molecular Growth Regulation,
National Institute of Child Health and Human Development, National
Institutes of Health, Bethesda, Maryland 20892-2753
Received 6 July 1998/Returned for modification 14 September
1998/Accepted 19 November 1998
Transcription factors of the interferon regulatory factor (IRF)
family bind to the type I interferon (IFN)-responsive element (ISRE)
and activate transcription from IFN-inducible genes. To identify
cofactors that associate with IRF proteins, DNA affinity binding assays
were performed with nuclear extracts prepared from tissue culture
cells. The results demonstrated that the endogenous IRFs bound to the
ISRE are complexed with the histone acetylases, PCAF, GCN5, and
p300/CREB binding protein and that histone acetylase activities are
accumulated on the IRF-ISRE complexes. By testing recombinant proteins,
we show that PCAF directly binds to some but not all members of the IRF
family through distinct domains of the two proteins. This interaction
was functionally significant, since transfection of PCAF strongly
enhanced IRF-1- and IRF-2-dependent promoter activities. Further
studies showed that expression of PCAF and other histone acetylases was
markedly induced in U937 cells upon phorbol ester treatment, which led
to increased recruitment of PCAF to the IRF-ISRE complexes. Coinciding
with the induction of histone acetylases, phorbol ester markedly
enhanced IFN-
-stimulated gene expression in U937 cells. Supporting
the role for PCAF in conferring IFN responsiveness, transfection of
PCAF into U937 cells led to a large increase in IFN-
-inducible
promoter activity. These results demonstrate that PCAF is a phorbol
ester-inducible coactivator of the IRF proteins which contributes to
the establishment of type I IFN responsiveness.
*
Corresponding author. Mailing address: Laboratory of
Molecular Growth Regulation, Bldg. 6, Rm. 2A01, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2735. Phone: (301) 496-9184. Fax: (301) 480-9354. E-mail: ozatok{at}nih.gov.

Present address: National Institute of Infectious Diseases, Tokyo
208,
Japan.
Molecular and Cellular Biology, March 1999, p. 1810-1820, Vol. 19, No. 3
0270-7306/99
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