Cell
Volume 111, Issue 5, 27 November 2002, Pages 621-633
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Differential Requirements for Runx Proteins in CD4 Repression and Epigenetic Silencing during T Lymphocyte Development

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Summary

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 CD4CD8+ cytotoxic cells. A stage-specific transcriptional silencer regulates expression of CD4 in both immature and CD4CD8+ 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. Runx1 is required for active repression in CD4CD8 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 CD8-lineage T lymphocytes.

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6

These authors contributed equally to this work.

7

Present address: Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.

8

Present address: Institute of Molecular and Cell Biology, National University of Singapore, 30 Medical Drive, Singapore 117609, Singapore.