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首页> 外文期刊>Nature immunology >Epigenetic repression of the Igk locus by STAT5-mediated recruitment of the histone methyltransferase Ezh2.
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Epigenetic repression of the Igk locus by STAT5-mediated recruitment of the histone methyltransferase Ezh2.

机译：STAT5介导的组蛋白甲基转移酶Ezh2募集的Igk基因座的表观遗传抑制。

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摘要

During B lymphopoiesis, recombination of the locus encoding the immunoglobulin kappa-chain complex (Igk) requires expression of the precursor to the B cell antigen receptor (pre-BCR) and escape from signaling via the interleukin 7 receptor (IL-7R). By activating the transcription factor STAT5, IL-7R signaling maintains proliferation and represses Igk germline transcription by unknown mechanisms. We demonstrate that a STAT5 tetramer bound the Igk intronic enhancer (E(kappai)), which led to recruitment of the histone methyltransferase Ezh2. Ezh2 marked trimethylation of histone H3 at Lys27 (H3K27me3) throughout the kappa-chain joining region (J(kappa)) to the kappa-chain constant region (C(kappa)). In the absence of Ezh2, IL-7 failed to repress Igk germline transcription. H3K27me3 modifications were lost after termination of IL-7R-STAT5 signaling, and the transcription factor E2A bound E(kappai), which resulted in acquisition of H3K4me1 and acetylated histone H4 (H4Ac). Genome-wide analyses showed a STAT5 tetrameric binding motif associated with transcriptional repression. Our data demonstrate how IL-7R signaling represses Igk germline transcription and provide a general model for STAT5-mediated epigenetic transcriptional repression.
机译：在B淋巴细胞生成过程中，编码免疫球蛋白kappa链复合体（Igk）的基因座重组需要B细胞抗原受体（pre-BCR）的前体表达，并通过白介素7受体（IL-7R）逃脱信号传导。通过激活转录因子STAT5，IL-7R信号传导可维持增殖并通过未知机制抑制Igk种系转录。我们证明，STAT5四聚体结合Igk内含子增强子（E（kappai）），从而导致组蛋白甲基转移酶Ezh2的募集。 Ezh2标记了在整个K链连接区（J（kappa））到K链恒定区（C（kappa））处Lys27（H3K27me3）处组蛋白H3的三甲基化。在没有Ezh2的情况下，IL-7不能抑制Igk种系转录。 IL-7R-STAT5信号终止后，H3K27me3修饰丢失，转录因子E2A结合E（kappai），导致获得H3K4me1和乙酰化组蛋白H4（H4Ac）。全基因组分析显示与转录抑制相关的STAT5四聚体结合基序。我们的数据证明IL-7R信号传导如何抑制Igk生殖系转录，并为STAT5介导的表观遗传转录抑制提供一般模型。

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