Myosin VI regulates gene pairing and transcriptional pause release in T cells

Proceedings of the National Academy of Sciences of the United States of America
Cornelia E ZorcaRichard A Flavell

Abstract

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-α, 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.

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Citations

May 11, 2016·Trends in Immunology·Bianca TesiYenan T Bryceson
Dec 1, 2017·Nature Communications·Natalia FiliChristopher P Toseland
Aug 5, 2017·Nature Structural & Molecular Biology·Ivan Krivega, Ann Dean
May 10, 2017·Nature Reviews. Genetics·Teddy JéguJeannie T Lee
Sep 9, 2017·The Journal of Biological Chemistry·Sarah M HeisslerJames R Sellers
Jul 12, 2017·Nature Structural & Molecular Biology·Hsueh-Ping ChuJeannie T Lee
Mar 19, 2020·Journal of Biomedical Science·Chia-Yu GuhHsueh-Ping Chu
Jun 6, 2020·Journal of Cell Science·Alexander W CookChristopher P Toseland
Nov 10, 2020·Current Opinion in Cell Biology·Audrey Yi Tyan PengBrian C Freeman
Apr 4, 2021·International Journal of Molecular Sciences·Ália Dos Santos, Christopher P Toseland
May 18, 2021·IScience·Matthias KneusselFrank F Heisler

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