Id helix-loop-helix proteins antagonize Pax transcription factor activity by inhibiting DNA binding

The Id subfamily of helix-loop-helix (HLH) proteins plays a fundamental rol e in the regulation of cellular proliferation and differentiation. The majo r mechanism by which Id proteins are thought to inhibit differentiation is through interaction with other HLH proteins and inhibition of their DNA-bin ding activity. However, Id proteins have also been shown to interact with o ther proteins involved in regulating cellular proliferation and differentia tion, suggesting a more widespread regulatory function. In this study we de monstrate functional interactions between Id proteins and members of the Pa x-2/-5/-8 subfamily of paired-domain transcription factors. Members of the Pax transcription factor family have key functions in regulating several de velopmental processes exemplified by B lymphopoiesis, in which Pax-5 plays an essential role. Id proteins bind to Pax proteins in vitro and in vivo. B inding occurs through the paired DNA-binding domain of the Pax proteins and results in the disruption of DNA-bound complexes containing Pax-2, Pax-5, and Pax-8. In vivo, Id proteins modulate the transcriptional activity media ted by Pax-5 complexes on the B-cell-specific mb-1 promoter. Our results th erefore demonstrate a novel facet of Id function in regulating cellular dif ferentiation by functionally antagonizing the action of members of the Pax transcription factor family.