Document Detail

Cd8 enhancer E8I and Runx factors regulate CD8α expression in activated CD8+ T cells.
MedLine Citation:
PMID:  22025728     Owner:  NLM     Status:  MEDLINE    
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.
Hammad Hassan; Shinya Sakaguchi; Mari Tenno; Aglaja Kopf; Nicole Boucheron; Andrea C Carpenter; Takeshi Egawa; Ichiro Taniuchi; Wilfried Ellmeier
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-10-24
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-09     Completed Date:  2012-01-25     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  18330-5     Citation Subset:  IM    
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria.
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MeSH Terms
Antigens, CD8 / genetics,  physiology*
CD8-Positive T-Lymphocytes / metabolism*
Chromatin Immunoprecipitation
Core Binding Factor Alpha 3 Subunit / genetics,  physiology*
Gene Expression
Histones / metabolism
Lymphocyte Activation
Promoter Regions, Genetic
Reg. No./Substance:
0/Antigens, CD8; 0/Core Binding Factor Alpha 3 Subunit; 0/Histones; 0/Runx3 protein, mouse

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