HEB Background Information Differentiation of myogenic cells is regulated by multiple positively and negatively acting factors. One well characterized family of helix-loop-helix (HLH) proteins known to play an important role in the regulation of muscle cell development includes Myo D, myogenin (1), Myf-5 (2) and Myf-6 (also designated MRF-4 or herculin) (3,4). Myo D transcription factors form heterodimers with products of a more widely expressed family of bHLH genes, the E family, which consists of at least three distinct genes: E2A, IF2 and HEB (5-8). Myo D-E heterodimers bind avidly to consensus (CANNTG) E box target sites that are functionally important elements in the upstream regulatory sequences of many muscle-specific terminal differentiation genes (5-8). Both homo- and hetero-oligomers of these proteins are able to distinguish very closely related E box proteins and are believed to play important roles in lineage specific gene expression.