| First Author | Zorca CE | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 13 | Pages | E1587-93 |
| PubMed ID | 25770220 | Mgi Jnum | J:220682 |
| Mgi Id | MGI:5635937 | Doi | 10.1073/pnas.1502461112 |
| Citation | Zorca CE, et al. (2015) Myosin VI regulates gene pairing and transcriptional pause release in T cells. Proc Natl Acad Sci U S A 112(13):E1587-93 |
| abstractText | Naive CD4 T cells differentiate into several effector lineages, which generate a stronger and more rapid response to previously encountered immunological challenges. Although effector function is a key feature of adaptive immunity, the molecular basis of this process is poorly understood. Here, we investigated the spatiotemporal regulation of cytokine gene expression in resting and restimulated effector T helper 1 (Th1) cells. We found that the Lymphotoxin (LT)/TNF alleles, which encode TNF-alpha, were closely juxtaposed shortly after T-cell receptor (TCR) engagement, when transcription factors are limiting. Allelic pairing required a nuclear myosin, myosin VI, which is rapidly recruited to the LT/TNF locus upon restimulation. Furthermore, transcription was paused at the TNF locus and other related genes in resting Th1 cells and released in a myosin VI-dependent manner following activation. We propose that homologous pairing and myosin VI-mediated transcriptional pause release account for the rapid and efficient expression of genes induced by an external stimulus. |
