染色质免疫沉淀
车站3
生物
分子生物学
CXCL11型
发起人
干扰素
癌症研究
基因表达调控
基因表达
基因
磷酸化
趋化因子
细胞生物学
病毒学
CXCL10型
遗传学
免疫系统
作者
Chuan Yang,Lai Wei,Susan R. Pfeffer,Ziyun Du,Aruna Murti,William J. Valentine,Yi Zheng,Lawrence M. Pfeffer
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2007-01-15
卷期号:178 (2): 986-992
被引量:46
标识
DOI:10.4049/jimmunol.178.2.986
摘要
IFNs selectively regulate gene expression through several signaling pathways. The present study explored the involvement of STAT3 in the IFN-induced expression of the gene encoding the CXCL11 chemokine. The CXCL11 gene was induced in IFN-sensitive Daudi cells, but not in an IFN-resistant DRST3 subline with a defective STAT3 signaling pathway. Although the IFN-stimulated gene ISG15 was induced to a similar extent in Daudi and DRST3 cells, expression of wild-type STAT3 in DRST3 cells restored the IFN inducibility of CXCL11. Reconstitution of STAT3 knockout mouse embryonic fibroblasts with wild-type STAT3, or STAT3 with the canonical STAT3 dimerization site at Y705 mutated, restored IFN inducibility of the CXCL11 gene. These data indicate that CXCL11 gene induction by IFN is STAT3 dependent, but that phosphorylation of Y705 of STAT3 is not required. Chromatin immunoprecipitation assays demonstrated that IFN treatment of Daudi and DRST3 cells induced STAT3 binding to the CXCL11 promoter. Chromatin immunoprecipitation assays also revealed that NF-kappaB family member p65 and IFN regulatory factor (IRF)1 were bound to CXCL11 promoter upon IFN treatment of Daudi cells. In contrast, IFN induced the binding of p50 and IRF2 to the CXCL11 promoter in DRST3 cells. The profile of promoter binding was indistinguishable in IFN-sensitive Daudi cells and DRST3 cells reconstituted with wild-type STAT3. Thus, STAT3 also plays a role in the recruitment of the transcriptional activators p65 and IRF1, and the displacement of the transcriptional repressors p50 and IRF2 from the CXCL11 promoter also appears to regulate the induction of CXCL11 gene transcription.
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