Publication Date:
2008-02-09
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Setoguchi, Ruka -- Tachibana, Masashi -- Naoe, Yoshinori -- Muroi, Sawako -- Akiyama, Kaori -- Tezuka, Chieko -- Okuda, Tsukasa -- Taniuchi, Ichiro -- New York, N.Y. -- Science. 2008 Feb 8;319(5864):822-5. doi: 10.1126/science.1151844.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Transcriptional Regulation, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18258917" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Differentiation
;
Cell Lineage
;
Chromatin Immunoprecipitation
;
Core Binding Factor Alpha 2 Subunit/genetics/*physiology
;
Core Binding Factor Alpha 3 Subunit/genetics/*physiology
;
Core Binding Factor beta Subunit/metabolism
;
Histocompatibility Antigens Class I/immunology
;
Histocompatibility Antigens Class II/immunology
;
Mice
;
Mice, Transgenic
;
Molecular Sequence Data
;
Silencer Elements, Transcriptional
;
T-Lymphocyte Subsets/cytology/*immunology/metabolism
;
T-Lymphocytes, Cytotoxic/cytology/*immunology/metabolism
;
T-Lymphocytes, Helper-Inducer/cytology/immunology/metabolism
;
Transcription Factors/genetics/*physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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