Beschreibung:
<jats:p>
<jats:italic>Cd8a</jats:italic>
and
<jats:italic>Cd8b1</jats:italic>
coreceptor gene (
<jats:italic>Cd8</jats:italic>
) expression is tightly controlled during T-cell development by the activity of five
<jats:italic>Cd8</jats:italic>
enhancers (
<jats:italic>
E8
<jats:sub>I</jats:sub>
–E8
<jats:sub>V</jats:sub>
</jats:italic>
). Here we demonstrate a unique transcriptional program regulating CD8 expression during CD8
<jats:sup>+</jats:sup>
effector T-cell differentiation. The
<jats:italic>Cd8</jats:italic>
enhancer
<jats:italic>
E8
<jats:sub>I</jats:sub>
</jats:italic>
and Runx/core-binding factor-β (CBFβ) complexes were required for the establishment of this regulatory circuit, because
<jats:italic>
E8
<jats:sub>I</jats:sub>
</jats:italic>
-, Runx3-, or CBFβ-deficient CD8
<jats:sup>+</jats:sup>
T cells down-regulated CD8α expression during activation. This finding correlated with enhanced repressive histone marks at the
<jats:italic>Cd8a</jats:italic>
promoter in the absence of
<jats:italic>
E8
<jats:sub>I</jats:sub>
</jats:italic>
, and the down-regulation of CD8α expression could be blocked by treating
<jats:italic>
E8
<jats:sub>I</jats:sub>
</jats:italic>
-, Runx3-, or CBFβ-deficient CD8
<jats:sup>+</jats:sup>
T cells with the histone deacetylase inhibitor trichostatin A. Moreover, Runx/CBFβ complexes bound the
<jats:italic>Cd8ab</jats:italic>
gene cluster in activated CD8
<jats:sup>+</jats:sup>
T cells, suggesting direct control of the
<jats:italic>Cd8a</jats:italic>
locus. However, CD8
<jats:sup>+</jats:sup>
effector T cells maintained high levels of CD8α when CBFβ was conditionally deleted after activation. Thus, our data suggest an
<jats:italic>
E8
<jats:sub>I</jats:sub>
</jats:italic>
- and Runx3/CBFβ-dependent epigenetic programming of the
<jats:italic>Cd8a</jats:italic>
locus during T-cell activation, leading to Runx/CBFβ complex-independent maintenance of CD8α expression in effector T cells.
</jats:p>