Runx3-mediated transcriptional program in cytotoxic lymphocytes.

Runx3-mediated transcriptional program in cytotoxic lymphocytes.
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DOI:
10.1371/journal.pone.0080467
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Groner Y
Groner Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lotem J;Levanon D;Negreanu V;Leshkowitz D;Friedlander G;Groner Y

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转录因子Runx 3在CD 8 + T细胞和NK细胞毒性淋巴细胞中高度表达,并且是其有效活化和增殖所必需的,但是在这些细胞中由Runx 3调节的转录程序的分子见解仍然缺失。使用Runx 3-ChIP-seq和野生型与Runx 3-/-原代细胞的转录组分析,我们现在已经在静息和IL-2激活状态下的两种细胞类型中鉴定了Runx 3调节的基因。Runx 3结合的基因组区域在这两种细胞类型位于相对于基因转录起始位点,并富集RUNX和ETS基序。结合的基因组区域显着重叠T-bet和p300结合的增强子区域Runx 3表达的Th 1辅助细胞。与静息细胞相比,IL-2激活的CD 8 + T细胞和NK细胞含有三倍多的Runx 3调节基因,这些基因是两种细胞类型共有的。共有的CD 8 + T和NK Runx 3调节基因的功能注释揭示了免疫相关术语的富集,包括淋巴细胞活化、增殖、细胞毒性、迁移和细胞因子产生,突出了Runx 3在CD 8 + T和NK活化细胞中的作用。
The transcription factor Runx3 is highly expressed in CD8+ T and NK cytotoxic lymphocytes and is required for their effective activation and proliferation but molecular insights into the transcription program regulated by Runx3 in these cells are still missing. Using Runx3-ChIP-seq and transcriptome analysis of wild type vs. Runx3-/- primary cells we have now identified Runx3-regulated genes in the two cell types at both resting and IL-2-activated states. Runx3-bound genomic regions in both cell types were distantly located relative to gene transcription start sites and were enriched for RUNX and ETS motifs. Bound genomic regions significantly overlapped T-bet and p300-bound enhancer regions in Runx3-expressing Th1 helper cells. Compared to resting cells, IL-2-activated CD8+ T and NK cells contain three times more Runx3-regulated genes that are common to both cell types. Functional annotation of shared CD8+ T and NK Runx3-regulated genes revealed enrichment for immune-associated terms including lymphocyte activation, proliferation, cytotoxicity, migration and cytokine production, highlighting the role of Runx3 in CD8+ T and NK activated cells.
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