Erschienen in:Proceedings of the National Academy of Sciences of the United States of America
Sprache:
Englisch
ISSN:
0027-8424
Entstehung:
Anmerkungen:
Beschreibung:
<p>Cd8a and Cd8b1 coreceptor gene (Cd8) expression is tightly controlled during T-cell development by the activity of five Cd8 enhancers (E8r-E8v). Here we demonstrate a unique transcriptional program regulating CD8 expression during CD8⁺ effector T-cell differentiation. The Cd8 enhancer E8, and Runx/core-binding factor-ß (CBFß) complexes were required for the establishment of this regulatory circuit because E8r, Runx3-, or CBFß-deficient CD8⁺ T cells down-regulated CD8α expression during activation. This finding correlated with enhanced repressive histone marks at the Cd8a promoter in the absence of E8₁. and the down-regulation of CD8γα expression could be blocked by treating E8r, Runx3-, or CBFßdeficient CD8⁺ T cells with the histone deacetylase inhibitor trichostatin A. Moreover, Runx/CBFß 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 CD8α when CBFß was conditionally deleted after activation. Thus, our data suggest an E8 r and Runx3/CBFß-dependent epigenetic programming of the Cd8a locus during T-cell activation, leading to Runx/CBFß complex-independent maintenance of CD8α expression in effector T cells.</p>