美国加州理工学院Ellen V. Rothenberg研究小组的发现表明Runx因子通过直接和基因网络依赖性机制启动T细胞和先天淋巴基序。相关论文于2023年8月10日发表于国际学术期刊《自然-免疫学》杂志。

研究人员表明小鼠早期T细胞发育中Runx的动态结合转移并不受局部染色质状态的限制，而受Runx剂量和功能伴侣的调节。在早期T祖细胞中Runx辅因子竞争招募有限的Runx因子库，并且在成熟前阶段，Runx蛋白可用性的适度增加会过早占据成熟后的结合位点。Runx因子可用性增加通过选择性激活T细胞身份和先天淋巴细胞程序导致T细胞谱系发育加速。这些程序由Runx与其他Runx诱导的转录因子共同调节，这些转录因子共同占据Runx靶基因并调控基因网络变化。

研究人员表示，Runx因子对各种造血细胞（包括T淋巴细胞）谱系特化至关重要。然而，它们调节环境特异性基因，并在不同细胞类型中占据不同的基因组区域。

附：英文原文

Title: Runx factors launch T cell and innate lymphoid programs via direct and gene network-based mechanisms

Author: Shin, Boyoung, Zhou, Wen, Wang, Jue, Gao, Fan, Rothenberg, Ellen V.

Issue&Volume: 2023-08-10

Abstract: Runx factors are essential for lineage specification of various hematopoietic cells, including T lymphocytes. However, they regulate context-specific genes and occupy distinct genomic regions in different cell types. Here, we show that dynamic Runx binding shifts in mouse early T cell development are mostly not restricted by local chromatin state but regulated by Runx dosage and functional partners. Runx cofactors compete to recruit a limited pool of Runx factors in early T progenitor cells, and a modest increase in Runx protein availability at pre-commitment stages causes premature Runx occupancy at post-commitment binding sites. This increased Runx factor availability results in striking T cell lineage developmental acceleration by selectively activating T cell-identity and innate lymphoid cell programs. These programs are collectively regulated by Runx together with other, Runx-induced transcription factors that co-occupy Runx-target genes and propagate gene network changes.

DOI: 10.1038/s41590-023-01585-z

Source: https://www.nature.com/articles/s41590-023-01585-z