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Cd8 enhancer E8I and Runx factors regulate CD8α expression in activated CD8+ T cells
Hammad Hassan1, Shinya Sakaguchi, Mari Tenno
1Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria.
Summary
CD8 coreceptor gene expression in T cells is regulated by enhancers and transcription factors. This study reveals epigenetic programming by E8(I) and Runx3/CBFβ complexes during T-cell activation for sustained CD8α expression.
Area of Science:
- Immunology
- Molecular Biology
- Epigenetics
Background:
- CD8 coreceptor gene (Cd8) expression is crucial for T-cell function and tightly regulated during development.
- Five Cd8 enhancers (E8(I)-E8(V)) control Cd8 expression during T-cell development.
Purpose of the Study:
- To elucidate the transcriptional program regulating CD8 expression during CD8(+) effector T-cell differentiation.
- To investigate the role of the Cd8 enhancer E8(I) and Runx/core-binding factor-β (CBFβ) complexes in this process.
Main Methods:
- Analysis of CD8(+) T cells deficient in E8(I), Runx3, or CBFβ.
- Assessment of histone marks at the Cd8a promoter.
- Treatment with histone deacetylase inhibitor trichostatin A.
- Chromatin immunoprecipitation to detect Runx/CBFβ complex binding.
Main Results:
- E8(I) and Runx/CBFβ complexes are essential for establishing CD8 expression during T-cell activation.
- Deficiency in E8(I), Runx3, or CBFβ leads to CD8α downregulation, associated with repressive histone marks.
- Histone deacetylase inhibition prevents CD8α downregulation in deficient cells.
- Runx/CBFβ complexes directly bind the Cd8a locus.
- CD8α expression is maintained independently of Runx/CBFβ after activation.
Conclusions:
- An E8(I)- and Runx3/CBFβ-dependent epigenetic program regulates the Cd8a locus during T-cell activation.
- This programming leads to sustained CD8α expression in effector T cells, independent of continuous Runx/CBFβ complex activity.
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