Differential Requirements for Runx Proteins in CD4 Repression and Epigenetic Silencing during T Lymphocyte Development
Copyright policy )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.
- National University of Singapore Singapore
- Kyushu University Japan
- Kyoto University Japan
- Howard Hughes Medical Institute United States
- Osaka University Japan
570, Biochemistry, Genetics and Molecular Biology(all), CD8 Antigens, T-Lymphocytes, Molecular Sequence Data, Gene Expression Regulation, Developmental, Cell Differentiation, CD8-Positive T-Lymphocytes, Mice, Mutant Strains, DNA-Binding Proteins, Repressor Proteins, Mice, Core Binding Factor Alpha 3 Subunit, CD4 Antigens, Animals, Humans, Point Mutation, Cell Lineage, Amino Acid Sequence, Gene Silencing, Cells, Cultured, T-Lymphocytes, Cytotoxic
570, Biochemistry, Genetics and Molecular Biology(all), CD8 Antigens, T-Lymphocytes, Molecular Sequence Data, Gene Expression Regulation, Developmental, Cell Differentiation, CD8-Positive T-Lymphocytes, Mice, Mutant Strains, DNA-Binding Proteins, Repressor Proteins, Mice, Core Binding Factor Alpha 3 Subunit, CD4 Antigens, Animals, Humans, Point Mutation, Cell Lineage, Amino Acid Sequence, Gene Silencing, Cells, Cultured, T-Lymphocytes, Cytotoxic
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).649 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 0.1%
Citations provided by BIP!Popularity provided by BIP!