Cd8 enhancer E8 Iand Runx factors regulate CD8α expression in activated CD8 + T cells

Hammad Hassan, Shinya Sakaguchi, Mari Tenno, Aglaja Kopf, Nicole Boucheron, Andrea C. Carpenter, Takeshi Egawa, Ichiro Taniuchi, Wilfried Ellmeier

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)18330-18335
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number45
DOIs
StatePublished - Nov 8 2011

Keywords

  • Cytotoxic T lymphocytes
  • Epigenetic marks
  • Transcriptional control

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    Hassan, H., Sakaguchi, S., Tenno, M., Kopf, A., Boucheron, N., Carpenter, A. C., Egawa, T., Taniuchi, I., & Ellmeier, W. (2011). Cd8 enhancer E8 Iand Runx factors regulate CD8α expression in activated CD8 + T cells. Proceedings of the National Academy of Sciences of the United States of America, 108(45), 18330-18335. https://doi.org/10.1073/pnas.1105835108