Cd8 enhancer E8I and Runx factors regulate CD8α expression in activated CD8+ T cells.
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-β (CBFβ) complexes were required for the establishment of this regulatory circuit, because E8(I)-, 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 E8(I), and the down-regulation of CD8α expression could be blocked by treating E8(I)-, 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 E8(I)- 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.
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology,  Medical University of Vienna, 1090 Vienna,  Austria.
Hammad
H
Hassan
Shinya
S
Sakaguchi
Mari
M
Tenno
Aglaja
A
Kopf
Nicole
N
Boucheron
Andrea C
AC
Carpenter
Takeshi
T
Egawa
Ichiro
I
Taniuchi
Wilfried
W
Ellmeier
D000818:Animals; D016827:CD8 Antigens / Q000235:genetics / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D006657:Histones / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D011401:Promoter Regions, Genetic
D016827:CD8 Antigens; D050677:Core Binding Factor Alpha 3 Subunit; D006657:Histones; C493730:Runx3 protein, mouse