Histone acetyltransferase activity of p300 enhances the activation of IL-18 promoter.
Interleukin-18 (IL-18), an important regulator of innate and acquired immune responses expressed from a variety of cell types, is a pleiotropic cytokine in the development of T helper type 1 (Thl) cells. The p300/CBP (CREB-binding protein) coactivator proteins are important histone acetyltransferases (HATs) that regulate the transcription of many genes. Whether p300/CBP play a role in the IL-18 expression has not been investigated previously. In this study, we analyzed the roles of p300 in the regulation of mouse IL-18 by using RT-PCR and a series of co-transfection studies. We showed that p300 had a stimulating effect on the endogenous IL-18 mRNA synthesis and on the activity of IL-18 p1 promoter. The results also showed that IL-18 p1 promoter activity was enhanced by p300 in a dose-dependent manner. Moreover, the p300-mediated activation function can be suppressed by the adenovirus E1A protein, which inhibits the HAT function of p300. Also, a mutation in p300 HAT region abolished the effect of p300 on IL-18 activation. These data further indicate that the acetylase activity of p300 was indispensable to its function. Furthermore, we found that p300 was able to enhance the effect of the transcription factor c-Fos on activation of the IL-18 promoter. Data presented in this paper implicate important roles of p300 in the transcriptional regulation of IL-18.
Sun
Haijing
H
Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, P.R. China.
Lu
Jun
J
Xu
Xin
X
Jin
Shunzi
S
Wang
Xiuli
X
Wei
Liang
L
Dong
Mei
M
Huang
Baiqu
B
D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism*; D017931:DNA Primers; D051548:Histone Acetyltransferases; D020382:Interleukin-18 / Q000235:genetics*; D051379:Mice; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D017931:DNA Primers; D051548:Histone Acetyltransferases; D020382:Interleukin-18; D012333:RNA, Messenger; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor