Tcra ENHANCER ACTIVITY DURING αβ T-cell DEVELOPMENT
The generation of αβ T-lymphocytes requires the construction of a T-cell receptor (TCR) complex through a highly ordered series of somatic rearrangement events at the Tcra and Tcrb loci during thymocyte development. Tcra enhancer (Eα) is essential for activation of germline transcription and VαJα gene segment recombination at the Tcra locus during thymocyte development. This enhancer influences chromatin structure across a 5OO-kb region in the Tcra locus.
My project is focused on the molecular mechanisms for Eα function during the development of αβ T-lymphocytes. My data indicate that binding of inducible transcription factors to an Eα enhanceosome previously assembled through the binding of constitutive and lymphoid specific-factors activates enhancer function during thymocyte development. Thus, the combinatorial assembly of tissue-and signal-specific transcription factors dictates Eα function in thymocytes. My current research tries to understand Eα function during development of αβ T-lymphocytes using different animal models to investigate whether Eα function is restricted to immature T-cells.