期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 45, 页码 18330-18335出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1105835108
关键词
epigenetic marks; transcriptional control; cytotoxic T lymphocytes
资金
- Austrian Science Fund [P16708, P19930, I698]
- Austrian Ministry of Science and Research (BM:WF) [Y-163]
- High Education Commission of Pakistan
- Leukemia and Lymphoma Society
- RIKEN Research Center for Allergy and Immunology
- Austrian Science Fund (FWF) [I 698] Funding Source: researchfish
- Austrian Science Fund (FWF) [P16708, I698, P19930] Funding Source: Austrian Science Fund (FWF)
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-beta (CBF beta) complexes were required for the establishment of this regulatory circuit, because E8(I)-, Runx3-, or CBF beta-deficient CD8(+) T cells down-regulated CD8 alpha 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 CD8 alpha expression could be blocked by treating E8I-, Runx3-, or CBF beta-deficient CD8(+) T cells with the histone deacetylase inhibitor trichostatin A. Moreover, Runx/CBF beta 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 CD8 alpha when CBF beta was conditionally deleted after activation. Thus, our data suggest an E8(I)- and Runx3/CBF beta-dependent epigenetic programming of the Cd8a locus during T-cell activation, leading to Runx/CBF beta complex-independent maintenance of CD8 alpha expression in effector T cells.
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