| First Author | He X | Year | 2008 |
| Journal | Immunity | Volume | 28 |
| Issue | 3 | Pages | 346-58 |
| PubMed ID | 18342007 | Mgi Jnum | J:132996 |
| Mgi Id | MGI:3777505 | Doi | 10.1016/j.immuni.2008.02.006 |
| Citation | He X, et al. (2008) CD4-CD8 lineage commitment is regulated by a silencer element at the ThPOK transcription-factor locus. Immunity 28(3):346-58 |
| abstractText | The transcription factor ThPOK is necessary and sufficient to trigger adoption of the CD4 lymphocyte fate. Here we investigate the regulation of ThPOK expression and its subsequent control of CD4+ T cell commitment. Treatment of immature thymocytes with anti-TCR (T cell receptor) showed that TCR signals were important in ThPOK induction and that the CD4+8lo stage was the likely target of the inductive TCR signal. We identified at the ThPOK locus a key distal regulatory element (DRE) that mediated its differential expression in class I- versus II-restricted CD4+8lo thymocytes. The DRE was both necessary for suppression of ThPOK expression in class I-restricted thymocytes and sufficient for its induction in class II-restricted thymocytes. Mutagenesis analysis defined an essential 80bp core DRE sequence and its potential regulatory motifs. We propose a silencer-dependent model of lineage choice, whereby inactivation of the DRE silencer by a strong TCR signal leads to CD4 commitment, whereas continued silencer activity leads to CD8 commitment. |
