Coactivator p300 acetylates the interferon regulatory factor-2 in U937 cells following phorbol ester treatment.
Interferon regulatory factor-2 (IRF-2) is a transcription factor of the IRF family that represses interferon-mediated gene expression. In the present study, we show that human monocytic U937 cells express truncated forms of IRF-2 containing the DNA binding domain but lacking much of the C-terminal regulatory domain. U937 cells are shown to respond to phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) to induce expression of histone acetylases p300 and p300/CBP-associated factor (PCAF). In addition, TPA treatment led to the appearance of full-length IRF-2, along with a reduction of the truncated protein. Interestingly, full-length IRF-2 in TPA-treated U937 cells occurred as a complex with p300 as well as PCAF and was itself acetylated. Consistent with these results, recombinant IRF-2 was acetylated by p300 and to a lesser degree by PCAF in vitro. Another IRF member, IRF-1, an activator of interferon-mediated transcription, was also acetylated in vitro by these acetylases. Finally, we demonstrate that the addition of IRF-2 but not IRF-1 inhibits core histone acetylation by p300 in vitro. The addition of IRF-2 also inhibited acetylation of nucleosomal histones in TPA-treated U937 cells. Acetylated IRF-2 may affect local chromatin structure in vivo by inhibiting core histone acetylation and may serve as a mechanism by which IRF-2 negatively regulates interferon-inducible transcription.
Masumi
A
A
Department of Safety Research on Biologics, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Ozato
K
K
D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D009687:Nuclear Proteins / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D020298:U937 Cells
D004268:DNA-Binding Proteins; D006657:Histones; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D009687:Nuclear Proteins; D009707:Nucleosomes; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D013755:Tetradecanoylphorbol Acetate