Following their first interaction with the antigen, quiescent naive T-helper (Th; CD4⁺) cells enlarge, differentiate, and proliferate; these processes are accompanied by substantial epigenetic alterations. We showed previously that the epigenetic regulators the polycomb-group (PcG) proteins have a dual function as both positive and negative transcriptional regulators; however, the underlying mechanisms remain poorly understood. Here, we demonstrate that during Th cell differentiation the methyltransferase activity of the PcG protein Ezh2 regulates post-transcriptionally inducible assembly of intranuclear actin filaments. These filaments are colocalized with the actin regulators Vav1 and WASp, vertically oriented to the T cell receptor, and intermingle with the chromatin fibers. Ezh2 and Vav1 are observed together at chromatin-actin intersections. Furthermore, the inducible assembly of nuclear actin filaments is required for chromatin spreading and nuclear growth. Altogether these findings delineate a model in which the epigenetic machinery orchestrates the dynamic mechanical force of the intranuclear cytoskeleton to reorganize chromatin during differentiation.

在第一次与抗原相互作用后，静止的幼稚 T-helper (Th; CD4 ⁺) 细胞增大、分化和增殖；这些过程伴随着大量的表观遗传改变。我们之前表明，多梳组（PcG）蛋白的表观遗传调节因子具有作为正转录调节因子和负转录调节因子的双重功能；然而，其潜在机制仍然知之甚少。在这里，我们证明在 Th 细胞分化过程中，PcG 蛋白 Ezh2 的甲基转移酶活性调节核内肌动蛋白丝的转录后诱导组装。这些细丝与肌动蛋白调节因子 Vav1 和 WASp 共定位，垂直定向于 T 细胞受体，并与染色质纤维混合。Ezh2 和 Vav1 在染色质-肌动蛋白交叉点处一起观察到。此外，核肌动蛋白丝的可诱导组装是染色质扩散和核生长所必需的。总之，这些发现描绘了一个模型，其中表观遗传机制协调核内细胞骨架的动态机械力以在分化过程中重组染色质。