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首页> 外文期刊>Nature immunology >Different molecular complexes that mediate transcriptional induction and repression by FoxP3
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Different molecular complexes that mediate transcriptional induction and repression by FoxP3

机译:不同的分子复合物,其介导转录诱导和抑制福索普3

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摘要

FoxP3 conditions the transcriptional signature and functional facets of regulatory T cells (T-reg cells). Its mechanism of action, whether as an activator or a repressor, has remained unclear. Here, chromatin analysis showed that FoxP3 bound active enhancer elements, not repressed chromatin, around loci over-or under-expressed in T-reg cells. We evaluated the impact of a panel of FoxP3 mutants on its transcriptional activity and interactions with DNA, transcriptional cofactors and chromatin. Computational integration, confirmed by biochemical interaction and size analyses, showed that FoxP3 existed in distinct multimolecular complexes. It was active and primarily an activator when complexed with the transcriptional factors RELA, IKZF2 and KAT5. In contrast, FoxP3 was inactive when complexed with the histone methyltransferase EZH2 and transcription factors YY1 and IKZF3. The latter complex partitioned to a peripheral region of the nucleus, as shown by super-resolution microscopy. Thus, FoxP3 acts in multimodal fashion to directly activate or repress transcription, in a context-and partner-dependent manner, to govern T-reg cell phenotypes.
机译:Foxp3条件调节T细胞(T-REG细胞)的转录签名和功能平面。其作用机制,无论是活化剂还是阻遏物,都仍然不清楚。这里,染色质分析表明,Foxp3结合的活性增强剂元素,不抑制染色质,在T-Reg细胞中过度或下表达的基因酯周围。我们评估了Foxp3突变体面板对其转录活动和与DNA,转录辅因子和染色质相互作用的影响。通过生化相互作用和尺寸分析证实的计算集成表明FOXP3存在于不同的多分子复合物中。当与转录因子rela,ikzf2和kat5复合时,它是活跃的,主要是活化剂。相比之下,与组蛋白甲基转移酶EzH2和转录因子YY1和IKZF3复合时,FoxP3在复合时无活性。后者复合物分离为细胞核的外周区域,如超分辨率显微镜所示。因此,Foxp3以多模式方式起作用,以语境和伴侣依赖性方式直接激活或抑制转录,以治理T-Reg细胞表型。

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