| First Author | Tanaka H | Year | 2013 |
| Journal | EMBO J | Volume | 32 |
| Issue | 8 | Pages | 1183-94 |
| PubMed ID | 23481257 | Mgi Jnum | J:195348 |
| Mgi Id | MGI:5478656 | Doi | 10.1038/emboj.2013.47 |
| Citation | Tanaka H, et al. (2013) Epigenetic Thpok silencing limits the time window to choose CD4(+) helper-lineage fate in the thymus. EMBO J 32(8):1183-94 |
| abstractText | 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. |
