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| Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development |
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| Author(s): Taniuchi I, Osato M, Egawa T, Sunshine MJ, Bae SC, Komori T, Ito Y, Littman DR |
| Source: CELL Volume: 111 Issue: 5 Pages: 621-633 Published: NOV 27 2002 |
| Times Cited: 254 References: 56 |
| Abstract: T lymphocytes differentiate in discrete stages within the thymus. Immature thymocytes lacking CD4 and CD8 coreceptors differentiate into double-positive cells (CD4(+)CD8(+)), which are selected to become either CD4(+)CD8(-)helper cells or CD4(-)CD8(+) cytotoxic cells. A stage-specific transcriptional silencer regulates expression of CD4 in both immature and CD4(-)CD8(+) thymocytes. We show here that binding sites for Runt domain transcription factors are essential for CD4 silencer function at both stages, and that different Runx family members are required to fulfill unique functions at each stage. Runxi is required for active repression in CD4(-)CD8(-) thymocytes whereas Runx3 is required for establishing epigenetic silencing in cytotoxic lineage thymocytes. Runx3-deficient cytotoxic T cells, but not helper cells, have defective responses to antigen, suggesting that Runx proteins have critical functions in lineage specification and homeostasis of CD8lineage T lymphocytes. |
| Document Type: Article |
| Language: English |
| Reprint Address: Taniuchi, I (reprint author), Kyushu Univ, Med Inst Bioregulat, Dept Mol Genet, Fukuoka 8128582, Japan |
Addresses:
1. NYU, Sch Med, Howard Hughes Med Inst, Mol Pathogenesis Program,Skirball Inst Biomol Med, New York, NY 10016 USA
2. Kyoto Univ, Inst Virus Res, Dept Viral Oncol, Kyoto 6068507, Japan
3. Chungbuk Natl Univ, Inst Tumor Res, Sch Med, Dept Biochem, Cheongju 361763, South Korea
4. Osaka Univ, Sch Med, Dept Mol Med, Osaka 5650871, Japan |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 621MV |
| ISSN: 0092-8674 |
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