美国国立卫生研究院Keji Zhao研究团队发现，组蛋白修饰与染色质相互作用调节T辅助细胞分化。2024年4月12日出版的《免疫》发表了这项成果。

研究人员对T辅助细胞（Th）分化过程中调控区域的动态组蛋白修饰，和染色质相互作用进行了绘制。数据显示，MLL4在初始CD4⁺T细胞中建立的H3K4me1图谱对于Th分化早期阶段，重组调控相互作用网络和协调基因表达至关重要。在Th2分化过程中，GATA3在进一步配置H3K4me1修饰和染色质相互作用网络方面起着至关重要的作用。

此外，研究人员还证明，HSS3锚定的染色质环限制了Th2基因座控制区（LCR）的活性，从而协调了Th2细胞因子的表达。这些研究结果为组蛋白修饰、染色质环和反式作用因子之间的相互作用，如何促进Th细胞分化的机制提供了见解。

据悉，免疫系统的发育和功能受时间空间基因表达程序的控制，而基因表达程序又受顺式调控元件、染色质结构和反式作用因子的调控。

附：英文原文

Title: Regulation of T helper cell differentiation by the interplay between histone modification and chromatin interaction

Author: Shuai Liu, Yaqiang Cao, Kairong Cui, Gang Ren, Tingting Zhao, Xuezheng Wang, Danping Wei, Zuojia Chen, Rama Krishna Gurram, Chengyu Liu, Chuan Wu, Jinfang Zhu, Keji Zhao

Issue&Volume: 2024-04-12

Abstract: The development and function of the immune system are controlled by temporospatialgene expression programs, which are regulated by cis-regulatory elements, chromatin structure, and trans-acting factors. In this study, we cataloged the dynamic histone modifications andchromatin 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 orchestratinggene expression during the early phase of Th differentiation. GATA3 plays a crucialrole in further configuring H3K4me1 modification and the chromatin interaction networkduring Th2 differentiation. Furthermore, we demonstrated that HSS3-anchored chromatinloops function to restrict the activity of the Th2 locus control region (LCR), thuscoordinating the expression of Th2 cytokines. Our results provide insights into themechanisms of how the interplay between histone modifications, chromatin looping,and trans-acting factors contributes to the differentiation of Th cells.

DOI: 10.1016/j.immuni.2024.03.018

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00139-0