Dual functions of Runx proteins for reactivating CD8 and silencing CD4 at the commitment process into CD8 thymocytes.
To understand how CD8 expression is regulated during the transition process from CD4+8+ (CD4 and CD8 double positive, DP) to CD4-8+ (CD8 single positive, CD8SP) cells in the thymus, the involvement of Runx proteins in the alteration of chromatin configuration was investigated. Using the chromatin immunoprecipitation assay, we first demonstrated that Runx proteins bind to the stage-specific CD8 enhancer, as well as the CD4 silencer, in CD8SP thymocytes. Among Runx family members, Runx3 expression was initiated in DP thymocytes receiving a positive selection signal and increased in concert with differentiation to the CD8SP stage. Furthermore, reactivation of the CD8 gene, as well as CD4 silencing, was suppressed in positively selected thymocytes of Runx dominant-negative transgenic mice. These results suggest that Runx proteins, especially Runx3, are involved in lineage specification of CD8 T cells and provide important information for understanding the mechanism for the mutually exclusive expression of coreceptors in mature thymocytes.
Sato
Takehito
T
Department of Immunology, Tokai University School of Medicine, Boseidai, Isehara, Kanagawa 259-1193, Japan.
Ohno
Shin-ichiro
S
Hayashi
Takumi
T
Sato
Chiharu
C
Kohu
Kazuyoshi
K
Satake
Masanobu
M
Habu
Sonoko
S
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D047369:Chromatin Immunoprecipitation; D002874:Chromosome Mapping; D050657:Core Binding Factor alpha Subunits; D017931:DNA Primers; D004742:Enhancer Elements, Genetic; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D020868:Gene Silencing / Q000276:immunology*; D015151:Immunoblotting; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology*; D009924:Organ Culture Techniques; D011948:Receptors, Antigen, T-Cell; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013950:Thymus Gland; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D050657:Core Binding Factor alpha Subunits; D017931:DNA Primers; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors