美国宾夕法尼亚大学佩雷尔曼医学院Golnaz Vahedi团队，合作揭示了TCF-1促进T细胞祖细胞中染色质跨拓扑关结合域的相互作用。相关论文于2022年6月20日发表于国际顶尖学术期刊《自然—免疫学》杂志上。

他们研究了TCF-1在三维 (3D)基因组重构中的作用。使用增益和功能丧失实验，他们发现TCF-1和结构蛋白CTCF的共占改变了T细胞祖细胞中拓扑相关域的结构，导致先前隔离的调节元件和靶基因之间的相互作用在 T 细胞发育的后期。长程相互作用中依赖于TCF-1的增益与活性增强子标记H3K27ac的沉积和活性增强子处黏附素负载因子 NIPBL的募集有关。这些数据表明，在T细胞发育过程中，TCF-1在控制全局性基因组组织方面发挥作用。

据悉，高迁移率组 (HMG) 转录因子TCF-1对于早期T细胞发育至关重要。尽管体外生化分析表明HMG蛋白可以作为高阶核组织组装中的结构元素，但TCF-1在T细胞发育过程中对控制3D基因组结构的贡献仍然未知。

附：英文原文

Title: TCF-1 promotes chromatin interactions across topologically associating domains in T cell progenitors

Author: Wang, Wenliang, Chandra, Aditi, Goldman, Naomi, Yoon, Sora, Ferrari, Emily K., Nguyen, Son. C., Joyce, Eric F., Vahedi, Golnaz

Issue&Volume: 2022-06-20

Abstract: The high mobility group (HMG) transcription factor TCF-1 is essential for early T cell development. Although in vitro biochemical assays suggest that HMG proteins can serve as architectural elements in the assembly of higher-order nuclear organization, the contribution of TCF-1 on the control of three-dimensional (3D) genome structures during T cell development remains unknown. Here, we investigated the role of TCF-1 in 3D genome reconfiguration. Using gain- and loss-of-function experiments, we discovered that the co-occupancy of TCF-1 and the architectural protein CTCF altered the structure of topologically associating domains in T cell progenitors, leading to interactions between previously insulated regulatory elements and target genes at late stages of T cell development. The TCF-1-dependent gain in long-range interactions was linked to deposition of active enhancer mark H3K27ac and recruitment of the cohesin-loading factor NIPBL at active enhancers. These data indicate that TCF-1 has a role in controlling global genome organization during T cell development. Vahedi and colleagues show that TCF-1 promotes T cell development by minimizing the spatial distance between regulatory elements that are located within insulated neighborhoods in progenitor cells and are required for the expression of T cell genes.

DOI: 10.1038/s41590-022-01232-z

Source: https://www.nature.com/articles/s41590-022-01232-z