EXPRESSION AND DISTINCT DNA-BINDING SPECIFICITY OF ME1A AND ME2 SUGGEST A UNIQUE ROLE DURING DIFFERENTIATION AND NEURONAL PLASTICITY

Class A basic-helix-loop-helix (bHLH) proteins have been referred to a s ubiquitous and are believed to have redundant functions. They are in volved in the control of several developmental pathways, such as neuro genesis and myogenesis. To rationalize the existence of multiple class A bHLH proteins, we evaluated the differences and similarities betwee n ME1a and ME2, two class A bHLH proteins, highly expressed in differe ntiating neuronal cells. In situ hybridization analyses reveal that ME 1a and ME2 are characterized by distinguishable patterns of expression in areas of the adult mouse brain where neuronal plasticity occurs. A lso, DNA-binding assays show that both proteins bind to E-boxes as hom odimers and heterodimers, and show differences in their DNA-binding sp ecificities, which suggest selective interactions with different bindi ng sites of target genes. In addition, in vitro DNA-binding assays dem onstrate that Id2 forms heterodimers with ME1a and ME2. As a result of these interactions, their DNA-binding activity is abolished. Furtherm ore, overexpression of Id2 in neuronal cells suppresses ME1a and ME2 t ranscriptional activity. Based on our data, we hypothesize that ME1a a nd ME2 may activate gene expression of different target genes and ther efore are likely to be differently involved during neurogenesis.