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 include Myo D, myogenin, Myf-5 and Myf-6 (also designated MRF-4 or herculin). 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. 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. Both homo- and heterooligomers 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.