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Epigenetic Thpok silencing limits the time window to choose CD4 + helper‐lineage fate in the thymus
Author(s) -
Tanaka Hirokazu,
Naito Taku,
Muroi Sawako,
Seo Wooseok,
Chihara Risa,
Miyamoto Chizuko,
Kominami Ryo,
Taniuchi Ichiro
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2013.47
Subject(s) - biology , transcriptional regulation , epigenetics , library science , genetics , gene , gene expression , computer science
CD4 + helper and CD8 + cytotoxic T cells differentiate from common precursors in the thymus after T‐cell receptor (TCR)‐mediated selection. Commitment to the helper lineage depends on persistent TCR signals and expression of the ThPOK transcription factor, whereas a ThPOK cis‐regulatory element, ThPOK silencer, represses Thpok gene expression during commitment to the cytotoxic lineage. Here, we show that silencer‐mediated alterations of chromatin structures in cytotoxic‐lineage thymocytes establish a repressive state that is epigenetically inherited in peripheral CD8 + T cells even after removal of the silencer. When silencer activity is enhanced in helper‐lineage cells, by increasing its copy number, a similar heritable Thpok silencing occurs. Epigenetic locking of the Thpok locus may therefore be an independent event from commitment to the cytotoxic lineage. These findings imply that long‐lasting TCR signals are needed to establish stable Thpok expression activity to commit to helper T‐cell fate and that full commitment to the helper lineage requires persistent reversal of silencer activity during a particular time window.