Publication Date:
2011-11-09
Description:
Cd8a and Cd8b1 coreceptor gene (Cd8) expression is tightly controlled during T-cell development by the activity of five Cd8 enhancers (E8I–E8V). Here we demonstrate a unique transcriptional program regulating CD8 expression during CD8+ effector T-cell differentiation. The Cd8 enhancer E8I and Runx/core-binding factor-β (CBFβ) complexes were required for the establishment of this regulatory circuit, because E8I-, Runx3-, or CBFβ-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 E8I, and the down-regulation of CD8α expression could be blocked by treating E8I-, Runx3-, or CBFβ-deficient CD8+ T cells with the histone deacetylase inhibitor trichostatin A. Moreover, Runx/CBFβ 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 CBFβ was conditionally deleted after activation. Thus, our data suggest an E8I- and Runx3/CBFβ-dependent epigenetic programming of the Cd8a locus during T-cell activation, leading to Runx/CBFβ complex-independent maintenance of CD8α expression in effector T cells.
Print ISSN:
0027-8424
Electronic ISSN:
1091-6490
Topics:
Biology
,
Medicine
,
Natural Sciences in General
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