Identification of a novel transcriptional activity of mammalian Id proteins

The Id proteins are a family of related mammalian helix-loop-helix (HLH) pr oteins which can interact with other HLH proteins but lack a basic region a nd are thus not thought to bind to DNA. Instead, they are hypothesized to a ct as dominant negative regulators of DNA-binding basic HLH (bHLH) proteins , by forming inactive heterodimers with these proteins. All four Id family proteins possess related HLH dimerization domains and can interact with sim ilar bHLH proteins, although with differing affinities. The functions of th e largely unrelated N- and C-terminal regions of the proteins are unknown. In this study, we have identified a novel transcriptional activity of the m ammalian Id proteins. We show that when fused to the heterologous GAL4 DNA- binding domain, all four of the mammalian Id proteins can activate GAL4-dep endent transcription. The HLH domain is necessary for the transactivation a ctivity observed, suggesting that interaction with a cellular HLH protein i s required. Co-transfection with exogenous Class A bHLH proteins (E-protein s) greatly potentiates the transactivation, which is abolished upon co-tran sfection with Class B bHLH proteins. These results are consistent with the idea that the Id proteins have a transcriptional activity when present in a DNA-binding complex.