Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development.
Journal:
Cell 2002 NovAuthors:
Taniuchi I, Osato M, Egawa T, Sunshine MJ, Bae SC, Komori T, Ito Y, Littman DR
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 bo
...[more]th 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.[less]
Mesh Headings:
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