Functional domains of Runx1 are differentially required for CD4 repression, TCRbeta expression, and CD4/8 double-negative to CD4/8 double-positive transition in thymocyte development.

Functional Domains of Runx1 Are Differentially Required for CD4 Repression, TCR Expression, and CD4/8 Double-Negative to CD4/8 Double-Positive Transition in Thymocyte Development

The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells

Members of the Runx family of transcriptional regulators are required for the appropriate expression of CD4 and CD8 at discrete stages of T cell development. The roles of these factors in other aspects of T cell development are unknown. We used a strategy to conditionally inactivate the genes encoding Runx1 or Runx3 at different stages of thymocyte development, demonstrating that Runx1 regulate...

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...

β-Selection: Abundance of TCRβ–/γδ– CD44–CD25– (DN4) cells in the foetal thymus

Expression of TCRbeta and pre-TCR signalling are essential for differentiation of CD4- CD8- double negative (DN) thymocytes to the CD4+ CD8+ double-positive (DP) stage. Thymocyte development in adult Rag1, Rag2 or TCRbetadelta-deficient mice is arrested at the DN3 stage leading to the assumption that pre-TCR signalling and beta-selection occur at, and are obligatory for, the transition from DN3...

Transcription factor AP4 modulates reversible and epigenetic silencing of the Cd4 gene.

CD4 coreceptor expression is negatively regulated through activity of the Cd4 silencer in CD4(-)CD8(-) double-negative (DN) thymocytes and CD8(+) cytotoxic lineage T cells. Whereas Cd4 silencing is reversed during transition from DN to CD4(+)CD8(+) double-positive stages, it is maintained through heritable epigenetic processes following its establishment in mature CD8(+) T cells. We previously ...