Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
PLoS One. 2013 Nov 13;8(11):e80467. doi: 10.1371/journal.pone.0080467. eCollection 2013.
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.
转录因子 Runx3 在 CD8(+) T 和 NK 细胞毒性淋巴细胞中高度表达，对于它们的有效激活和增殖是必需的，但对于 Runx3 在这些细胞中调节的转录程序的分子见解仍然缺失。使用 Runx3-ChIP-seq 和野生型与 Runx3(-/-)原代细胞的转录组分析，我们现在已经在两种细胞类型的静止和 IL-2 激活状态下鉴定了 Runx3 调节的基因。两种细胞类型中 Runx3 结合的基因组区域相对于基因转录起始位点距离较远，并且富含 RUNX 和 ETS 基序。在表达 Runx3 的 Th1 辅助细胞中，结合的基因组区域与 T-bet 和 p300 结合的增强子区域显著重叠。与静止细胞相比，IL-2 激活的 CD8(+) T 和 NK 细胞包含三倍数量的共同存在于两种细胞类型中的 Runx3 调节基因。共享的 CD8(+) T 和 NK Runx3 调节基因的功能注释显示出与免疫相关术语的富集，包括淋巴细胞激活、增殖、细胞毒性、迁移和细胞因子产生，突出了 Runx3 在 CD8(+) T 和 NK 激活细胞中的作用。
