The Tal1 gene (also called Scl or TCL5) encodes a basic helix-loop-helix transcription factor required for hematopoiesis and vasculogenesis. Additionally, aberrant transcriptional activation of the Tal1 gene is a frequent event in human T cell acute lymphoblastic leukemia (T-ALL). T cell specific expression of TAL1 in mice induces aggressive T cell malignancies, demonstrating the oncogenic potential of TAL1. Yet, the underlying mechanisms of TAL1 induced tumorigenesis are poorly understood. By inhibiting E protein mediated transcription of the pTalpha gene, TAL1 can interfere with the T cell differentiation program. In addition, several studies suggest that TAL1 expression might also enhance proliferation rate. We report here that TAL1 can bind the E boxes in both the p16 and the pTalpha promoters, and functionally suppress the activity of both promoters. These results indicate that TAL1 can affect both T cell proliferation and differentiation. Moreover, we show that overexpression of TAL1 in hematopoietic progenitor cells promotes cell cycle division.