| First Author | Hassan H | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 45 | Pages | 18330-5 |
| PubMed ID | 22025728 | Mgi Jnum | J:180248 |
| Mgi Id | MGI:5305899 | Doi | 10.1073/pnas.1105835108 |
| Citation | Hassan H, et al. (2011) Cd8 enhancer E8I and Runx factors regulate CD8alpha expression in activated CD8+ T cells. Proc Natl Acad Sci U S A 108(45):18330-5 |
| abstractText | Cd8a and Cd8b1 coreceptor gene (Cd8) expression is tightly controlled during T-cell development by the activity of five Cd8 enhancers (E8(I)-E8(V)). Here we demonstrate a unique transcriptional program regulating CD8 expression during CD8(+) effector T-cell differentiation. The Cd8 enhancer E8(I) and Runx/core-binding factor-beta (CBFbeta) complexes were required for the establishment of this regulatory circuit, because E8(I)-, Runx3-, or CBFbeta-deficient CD8(+) T cells down-regulated CD8alpha expression during activation. This finding correlated with enhanced repressive histone marks at the Cd8a promoter in the absence of E8(I), and the down-regulation of CD8alpha expression could be blocked by treating E8(I)-, Runx3-, or CBFbeta-deficient CD8(+) T cells with the histone deacetylase inhibitor trichostatin A. Moreover, Runx/CBFbeta complexes bound the Cd8ab gene cluster in activated CD8(+) T cells, suggesting direct control of the Cd8a locus. However, CD8(+) effector T cells maintained high levels of CD8alpha when CBFbeta was conditionally deleted after activation. Thus, our data suggest an E8(I)- and Runx3/CBFbeta-dependent epigenetic programming of the Cd8a locus during T-cell activation, leading to Runx/CBFbeta complex-independent maintenance of CD8alpha expression in effector T cells. |
