Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T cell development.
Mouse CD4+CD8+ double-positive (DP) thymocytes differentiate into CD4+ helper-lineage cells upon expression of the transcription factor Th-POK but commit to the CD8+ cytotoxic lineage in its absence. We report the redirected differentiation of class I-restricted thymocytes into CD4+CD8- helper-like T cells upon loss of Runx transcription factor complexes. A Runx-binding sequence within the Th-POK locus acts as a transcriptional silencer that is essential for Th-POK repression and for development of CD8+ T cells. Thus, Th-POK expression and genetic programming for T helper cell development are actively inhibited by Runx-dependent silencer activity, allowing for cytotoxic T cell differentiation. Identification of the transcription factors network in CD4 and CD8 lineage choice provides insight into how distinct T cell subsets are developed for regulating the adaptive immune system.
Setoguchi
Ruka
R
Laboratory for Transcriptional Regulation, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
Tachibana
Masashi
M
Naoe
Yoshinori
Y
Muroi
Sawako
S
Akiyama
Kaori
K
Tezuka
Chieko
C
Okuda
Tsukasa
T
Taniuchi
Ichiro
I
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D047369:Chromatin Immunoprecipitation; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000502:physiology*; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000502:physiology*; D050658:Core Binding Factor beta Subunit / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D037941:Silencer Elements, Transcriptional; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D050658:Core Binding Factor beta Subunit; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D014157:Transcription Factors; C493693:Cbfb protein, mouse; C493726:Runx1 protein, mouse; C493730:Runx3 protein, mouse; C497211:Zbtb7b protein, mouse