POSITIVE AND NEGATIVE TRANSCRIPTIONAL CONTROL BY THE TAL1 HELIX-LOOP-HELIX PROTEIN

Tumor-specific activation of the TAL1 gene is the most common genetic defect associated with T-cell acute lymphoblastic leukemia. The TAL1 g ene products possess a basic helix-loop-helix (bHLH) moth, a protein-d imerization and DNA-binding domain found in several transcription fact ors. TAL1 polypeptides interact, in vitro and in vivo, with class A bH LH proteins (e.g., E47) to form heterodimers with sequence-specific DN A-binding activity. In this study, we show that TAL1 can regulate the transcription of an artificial reporter gene that contains binding sit es for bHLH heterodimers involving TAL1. Transcription of the reporter is strongly induced by E47-E47 homodimers and moderately induced by T AL1-E47 heterodimers. Thus, in a cellular environment that allows form ation of E47-E47 homodimers (e.g., in the absence of Id regulatory pro teins) TAL1 can repress transcription by recruiting E47 into bHLH comp lexes with less transcriptional activity (i.e., TAL1-E47 heterodimers) . However, in other settings TAL1 can activate transcription because T AL1-E47 heterodimers are more resistant to negative regulation by Id p roteins. Hence, TAL1 can potentially regulate transcription in either a positive or negative fashion.