2002 Fiscal Year Final Research Report Summary
The biological mechanism of Interferon Regulatory Factors
| Project/Area Number |
13672320
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | National Institute of infectious Diseases |
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Principal Investigator |
MASUMI Atsuko National Institute of Infectious Diseases, Department of Safety Research on Biologics, Senior Scientist., 血液・安全性研究部, 主任研究官 (70165728)
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| Project Period (FY) |
2001 – 2002
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| Keywords | IRF / Acetylation / Chromatin / cell growth / Interferon |
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| Research Abstract |
We have previously shown that interferon regulatory factor-2 (IRF-2) is acetylated by p300 and PCAF in vivo and in vitro. In this study we identified, by mass spectrometry, two lysine residues in the DNA binding domain (DBD), K75 and K78, to be the major acetylation sites in IRF-2. Although acetylation of IRF-2 did not alter DNA binding activity in vitro, mutation of K75 diminished IRF-2 dependent activation of histone H4 promoter activity. Acetylation of IRF-2 and IRF-2-stimulated H4 promoter activity were inhibited by the adenovirus E1A, indicating the involvement of p300/CBP. Mutation of K78, a residue conserved throughout the IRF family members, led to the abrogation of DNA binding activity independently of acetylation. H4 is transcribed only in rapidly growing cells and its promoter activity is dependent on cell growth. Consistent with a role for acetylated IRF-2 in cell growth control, IRF-2 was acetylated only in growing NIH 3T3 cells, but not in growth-arrested counterparts. Chromatin immunoprecipitation assays showed that IRF-2 interacted with p300 and bound to the endogenous H4 promoter only in growing cells, although the levels of total IRF-2 were comparable in both growing and growth-arrested cells. These results indicate that IRF-2 is acetylated in a cell growth-dependent manner, which enables it to contribute to transcription of cell growth regulated promoters.
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