Direct involvement of CREB-binding protein/p300 in sequence-specific DNA binding of virus-activated interferon regulatory factor-3 holocomplex.
Infections of bacteria and viruses induce host defense reactions known as innate responses including the activation of interferon regulatory factor-3 (IRF-3), critical for the activation of type I interferon system. Upon immediate early signals triggered by the infection, IRF-3 is phosphorylated and a homodimer results. The homodimer complexes with the coactivator CREB-binding protein (CBP)/p300 in the nucleus; thus, holocomplex of IRF-3 competent in DNA binding is generated. We showed CBP/p300 to be indispensable for the DNA binding activity of the holocomplex and to aid the binding through direct interaction with the DNA. We demonstrated that p300 binds with the IRF-3 homodimer via a Q-rich domain and that an intact histone acetyltransferase (HAT) domain is indispensable for the DNA binding of the holocomplex along with a CH3 domain, which connects the HAT and Q-rich domains. These results highlight a novel function of CBP/p300: direct involvement in sequence-specific DNA binding. Furthermore, the critical function of these domains in virus-induced gene activation was demonstrated in vivo by using p300 mutants.
Suhara
Wakako
W
Department of Tumor Cell Biology, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
Yoneyama
Mitsutoshi
M
Kitabayashi
Issay
I
Fujita
Takashi
T
D000123:Acetyltransferases / Q000737:chemistry* / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000494:pharmacology; D019281:Dimerization; D005982:Glutathione Transferase / Q000378:metabolism / Q000494:pharmacology; D005990:Glycerol / Q000494:pharmacology; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D015151:Immunoblotting; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014466:Ultraviolet Rays; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D003840:Deoxycholic Acid; D005982:Glutathione Transferase; D005990:Glycerol; D051548:Histone Acetyltransferases; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C494232:IRF3 protein, human; C494233:Irf3 protein, mouse