Cutting Edge: The Histone Methyltransferase G9a Is Required for Silencing of Helper T Lineage-Associated Genes in Proliferating CD8 T Cells.

Cutting Edge: The Histone Methyltransferase G9a Is Required for Silencing of Helper T Lineage-Associated Genes in Proliferating CD8 T Cells.
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DOI:
10.4049/jimmunol.1701700
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发表时间:
2018-06-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Egawa T
Egawa T
中科院分区:
其他
文献类型:
--
作者:
Verbaro DJ;Sakurai N;Kim B;Shinkai Y;Egawa T

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胸腺中辅助性T细胞与细胞毒性T细胞的谱系决定已经被作为沉默替代谱系基因的模型进行了研究。虽然转录因子RUNX3在发育中的CD8T细胞中启动CD4沉默是必需的,但目前尚不清楚CD4和其他辅助T细胞系基因的沉默是如何维持的。我们发现组蛋白甲基转移酶G9a对于沉默增殖中的小鼠CD8T细胞中的辅助性T细胞系基因是必需的。尽管最初正常的CD4下调,G9a缺陷的CD8T细胞在淋巴细胞减少的重复分裂或对肿瘤抗原的反应中去抑制CD4和其他辅助谱系基因。然而,对于对单核细胞增多性李斯特菌感染有反应的CD8T细胞中的那些基因的持续沉默来说,G9a是必不可少的。这些结果表明,G9a有助于在细胞分裂过程中维持CD8T细胞的细胞特性,而炎症信号进一步加强了这种特性。
Helper versus cytotoxic T lineage decision in the thymus has been studied as a model for silencing of alternative lineage genes. While the transcription factor RUNX3 is required for the initiation of Cd4 silencing in developing CD8 T cells, it is unknown how silencing of Cd4 and other helper T lineage genes is maintained. We show that the histone methyltransferase G9a is necessary for silencing of helper T lineage genes in proliferating mouse CD8 T cells. Despite normal initial Cd4 downregulation, G9a-deficient CD8 T cells de-repress Cd4 and other helper lineage genes during repeated division in lymphopenia or in response to tumor Ag. However, G9a was dispensable for continued silencing of those genes in CD8 T cells that respond to infection by L. monocytogenes. These results demonstrate that G9a facilitates maintenance of cellular identity of CD8 T cells during cell division, which is further reinforced by inflammatory signals.
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