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.

高迁移率基团 (HMG) 转录因子 TCF-1 对于早期 T 细胞发育至关重要。尽管体外生化测定表明 HMG 蛋白可以作为高级核组织组装中的结构元件，但 TCF-1 在 T 细胞发育过程中控制三维 (3D) 基因组结构的贡献仍然未知。在这里，我们研究了 TCF-1 在 3D 基因组重构中的作用。通过功能获得和功能丧失实验，我们发现 TCF-1 和结构蛋白 CTCF 的共存改变了 T 细胞祖细胞中拓扑关联结构域的结构，导致先前绝缘的调节元件和靶基因之间的相互作用处于 T 细胞发育的后期。长程相互作用中 TCF-1 依赖性增益与活性增强子标记 H3K27ac 的沉积和活性增强子处粘连蛋白负载因子 NIPBL 的募集有关。这些数据表明 TCF-1 在 T 细胞发育过程中具有控制全局基因组组织的作用。