Research Track

Lymphocyte differentiation proceeds through multiple stages characterized by the expression of distinct sets of genes. Our goals include understanding how Early B cell Factor (EBF), Runx1 and Pax5 regulate B lineage specification and lineage commitment. EBF is a DNA-binding protein required for B cell lymphopoiesis and expression of proteins essential for B cell receptor function. The absence of EBF results in a developmental blockade at a pre-pro-B cell-like stage resulting in a complete lack of functional B cells and immunoglobulins. In accord with these observations, we have elucidated a central role of EBF in the specification of B lineage cells. We defined a new function of EBF as a ‘pioneer’ of epigenetic modifications necessary for gene activation. These modifications are necessary for the function of other transcriptional regulators, including Pax5. Our observations suggest a molecular basis for EBF’s role in the hierarchical network of factors necessary for B lymphopoiesis. More recently we defined functions of EBF as a negative regulator of non-B cell gene programs. We are currently continuing our studies by using molecular techniques and animal model systems to understand how EBF initiates the remodeling of chromatin, DNA demethylation and the control of B cell identity.