ROLE OF THE E2A BHLH PROTEINS IN B LYMPHOCYTE COMMITMENT

University Of Pennsylvania, Philadelphia PA

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Abstract

Description (taken directly from the application): The E2A proteins, E12, and E47 (E2- 5), are members of the basic-Helix-Loop-Helix (bHLH) family of DNA binding proteins. Encoded by the E2A gene, they are ubiquitously expressed, but have also been shown to be mediate B cell-specific transcriptional activation by the immunoglobulin heavy chain enhancer. Moreover, evidence from E2A-deficient mice indicates that the proteins are absolutely necessary for the generation and/or maintenance of B cells. E47 is inactivated in a variety of non-B cells by mechanisms that include the phosphorylation of serines adjacent to the bHLH domain. This proposal aims to study the consequences of constitutively expressing E2A proteins. The question being addressed is: To what extent are the E2A proteins sufficient for B cell determination? In particular, the effects of constitutively-expressed E2A proteins will be examined in a) transiently-transfected non-B cell lines, b) stably-transformed B X T hybrid cells, and c) transgenic mice that express the proteins in targeted cell types including B and T lymphocytes. We will also identify novel E2A protein-induced genes.