| First Author | Titelbaum M | Year | 2021 |
| Journal | iScience | Volume | 24 |
| Issue | 10 | Pages | 103093 |
| PubMed ID | 34622148 | Mgi Jnum | J:314365 |
| Mgi Id | MGI:6780786 | Doi | 10.1016/j.isci.2021.103093 |
| Citation | Titelbaum M, et al. (2021) Ezh2 harnesses the intranuclear actin cytoskeleton to remodel chromatin in differentiating Th cells. iScience 24(10):103093 |
| abstractText | 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. |
