Histone acetyltransferase activity of p300 enhances the activation of IL-12 p40 promoter.
Interleukin-12 (IL-12) is a heterodimeric cytokine produced by macrophages in response to intracellular pathogens and provides an obligatory signal for the differentiation of T-helper-1 cells. p300 is an important histone acetyltransferase (HAT) and has been implicated in the regulation of gene expression. Whether p300 plays a role in the IL-12 expression has not been investigated before. In this study, we analyzed the roles of p300 in the regulation of human IL-12 p40. By using RT-PCR and a series of co-transfection studies, we found that p300 had a stimulating effect on the expression of endogenous IL-12 p40 mRNA and on the activity of IL-12 p40 promoter. We also showed that the HAT activity of p300 was essential to its function in regulating IL-12 promoter, since the mutant p300 with the HAT domain deleted did not have such a stimulation effect. In addition, the adenovirus E1A protein suppressed the p300 function, whereas the mutant E1A lacking the p300 interaction domain did not. Furthermore, p300 was able to reinforce the c-Rel-mediated activation of IL-12 p40. Results presented in this paper implicate that p300 is involved in the transcriptional regulation of IL-12 p40, and IL-12 p40 is one of the target genes of p300.
Sun
Haijing
H
Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
Lu
Jun
J
Wei
Liang
L
Wang
Xiuli
X
Xu
Xin
X
Dong
Mei
M
Huang
Baiqu
B
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D017500:Adenovirus E1A Proteins / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D051548:Histone Acetyltransferases; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics*; D053762:Interleukin-12 Subunit p40; D011401:Promoter Regions, Genetic; D021122:Protein Subunits / Q000235:genetics*; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors; D015533:Transcriptional Activation; D014162:Transfection; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D017500:Adenovirus E1A Proteins; D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D018664:Interleukin-12; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D020569:Proto-Oncogene Proteins c-rel; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor