The development and function of the immune system are controlled by temporospatial gene expression programs, which are regulated by cis-regulatory elements, chromatin structure, and trans-acting factors. In this study, we cataloged the dynamic histone modifications and chromatin interactions at regulatory regions during T helper (Th) cell differentiation. Our data revealed that the H3K4me1 landscape established by MLL4 in naive CD4⁺ T cells is critical for restructuring the regulatory interaction network and orchestrating gene expression during the early phase of Th differentiation. GATA3 plays a crucial role in further configuring H3K4me1 modification and the chromatin interaction network during Th2 differentiation. Furthermore, we demonstrated that HSS3-anchored chromatin loops function to restrict the activity of the Th2 locus control region (LCR), thus coordinating the expression of Th2 cytokines. Our results provide insights into the mechanisms of how the interplay between histone modifications, chromatin looping, and trans-acting factors contributes to the differentiation of Th cells.

免疫系统的发育和功能受时空基因表达程序控制，而时空基因表达程序受顺式调节元件、染色质结构和反式作用因子的调节。在这项研究中，我们对 T 辅助细胞 (Th) 细胞分化过程中调节区域的动态组蛋白修饰和染色质相互作用进行了分类。我们的数据显示，MLL4 在初始 CD4 ⁺ T 细胞中建立的 H3K4me1 景观对于在 Th 分化的早期阶段重建调控相互作用网络和协调基因表达至关重要。 GATA3 在 Th2 分化过程中进一步配置 H3K4me1 修饰和染色质相互作用网络中发挥着至关重要的作用。此外，我们证明HSS3锚定染色质环可限制Th2基因座控制区（LCR）的活性，从而协调Th2细胞因子的表达。我们的结果提供了关于组蛋白修饰、染色质环和反式作用因子之间的相互作用如何促进 Th 细胞分化的机制的见解。