车站2
STAT1
生物
酪氨酸激酶2
组蛋白H3
信号转导
细胞生物学
贾纳斯激酶
组蛋白
H3K4me3
STAT6
磷酸化
受体
癌症研究
STAT蛋白
发起人
车站3
免疫学
细胞因子
基因表达
生物化学
白细胞介素4
基因
血小板源性生长因子受体
生长因子
作者
Chulbul M. Ahmed,Ezra N. Noon-Song,Kaisa Kemppainen,Massimo P. Pascalli,Howard M. Johnson
标识
DOI:10.1016/j.jneuroim.2012.10.006
摘要
Recent studies have suggested that activated wild-type and mutant Janus kinase JAK2 play a role in the epigenetics of histone modification, where it phosphorylates histone H3 on tyrosine 41(H3pY41). We showed that type I IFN signaling involves activated TYK2 in the nucleus. ChIP-PCR demonstrated the presence of receptor subunits IFNAR1 and IFNAR2 along with TYK2, STAT1, and H3pY41 specifically at the promoter of the OAS1 gene in IFN treated cells. A complex of IFNAR1, TYK2, and STAT1α was also shown in the nucleus by immunoprecipitation. IFN treatment was required for TYK2 activation in the nucleus. The presence of IFNAR1, IFNAR2, and activated STAT1 and STAT2, as well as the type I IFN in the nucleus of treated cells was confirmed by the combination of Western blotting and confocal microscopy. Trimethylated histone H3 lysine 9 underwent demethylation and subsequent acetylation specifically in the region of the OAS1 promoter. Resultant N-terminal truncated IFN mimetics functioned intracellularly as antivirals as well as therapeutics against experimental allergic encephalomyelitis without the undesirable side effects that limit the therapeutic efficacy of IFNβ in treatment of multiple sclerosis. The findings indicate that IFN signaling is complex like that of steroid signaling.
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