Ezh2 harnesses the intranuclear actin cytoskeleton to remodel chromatin in differentiating Th cells

• Main Authors: Moran Titelbaum, Boris Brant, Daniel Baumel, Alina Burstein-Willensky, Shira Perez, Yiftah Barsheshet, Orly Avni
• Format: Article
• Language: English
• Published: Elsevier 2021-10-01
• Series: iScience
• Subjects: Immunology; Biological sciences; Cell biology
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004221010610

Summary: 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.