Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development.
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. Runx1 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 CD8-lineage T lymphocytes.
Pubmed ID: 12464175 RIS Download
Amino Acid Sequence | Animals | Antigens, CD4 | Antigens, CD8 | CD8-Positive T-Lymphocytes | Cell Differentiation | Cell Lineage | Cells, Cultured | Core Binding Factor Alpha 3 Subunit | DNA-Binding Proteins | Gene Expression Regulation, Developmental | Gene Silencing | Humans | Mice | Mice, Mutant Strains | Molecular Sequence Data | Point Mutation | Repressor Proteins | T-Lymphocytes | T-Lymphocytes, Cytotoxic | Thymus Gland | Transcription Factors