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.
journal_name
Proc Natl Acad Sci U S Aauthors
Zorca CE,Kim LK,Kim YJ,Krause MR,Zenklusen D,Spilianakis CG,Flavell RAdoi
10.1073/pnas.1502461112subject
Has Abstractpub_date
2015-03-31 00:00:00pages
E1587-93issue
13eissn
0027-8424issn
1091-6490pii
1502461112journal_volume
112pub_type
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