Regulation of early lymphocyte development by E2A family proteins

Lymphocytes develop from hematopoietic stem cells through a series of highly regulated differentiation events in the bone marrow and thymus. A number of transcription factors are known to collaborate in controlling the timing and specificity of gene expression required for these developmental processes to occur. The basic helix-loop-helix (bHLH) proteins encoded by the E2A gene have been shown to play particularly important roles in the initiation and progression of lymphocyte differentiation. Gene targeting experiments in mice have demonstrated a requirement for E2A proteins at the onset of B lymphocyte development. More recent studies have broadened our view on the function of E2A proteins at multiple stages of lymphopoiesis and in the regulation of lymphoid-specific gene expression. Here we review the mammalian E2A proteins and the accumulated evidence demonstrating central roles for E2A throughout early B and T lymphocyte development. We also speculate on the direction of future research on the mechanisms underlying the lineage and stage-specific functions of E2A in lymphopoiesis.