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

摘要: Runx1 (AML1) has multiple functions in thymocyte development, including CD4 repression immature thymocytes, expression of TCRβ, and efficient β-selection. To determine the functional domains important for we cultured Runx1-deficient murine fetal liver (FL) cells on OP9-Delta-like 1 stromal cells, which express Delta-like support development vitro, introduced or C-terminal-deletion mutants into FL by retrovirus infection. In this system, failed to follow normal whereas introduction was sufficient produce that indistinguishable from wild-type cells. contrast, lacked activation domain necessary initiating gene transcription did not fully restore differentiation, it neither repressed nor promoted CD4/8 double-negative double-positive transition. Although C-terminal VWRPY motif-deficient mutant Runx1, cannot interact with transcriptional corepressor Transducin-like enhancer split (TLE), transition, efficiently repress expression. These results suggest is essential establish both TLE-dependent TLE-independent development.