Introduction

Abstract The transcription of genes within eukaryotic cells is controlled by complex interactions between transcription factors and specific DNA recognition sequences in target genes. These DNA-binding transcription factors fall into a number of groups, each defined by shared sequence and, presumably structural, motifs. One such motif is the helix-loop-helix (HLH), first identified in an immunoglobulin enhancer-binding polypeptide as well as several other proteins known, or suspected, to be transcription factors [741]. The HLH region has also sometimes been referred to as the ‘Myc homology domain’, doubtless in deference to the notoriety and perceived importance of Myc proteins in carcinogenesis. However, the HLH motif is present in many proteins of diverse biological function and unified only by their common involvement in transcriptional regulation (reviewed in [3, 4, 32, 34, 43, 51, 62, 64, 69, 1312]). The HLH domain is a dimerization domain that mediates homo- and/or hetero-dimerization with other HLH proteins. The HLH domain is usually adjacent to a short region of basic residues that constitutes the sequence-specific DNA interaction interface; hence such proteins are often referred to as bHLH proteins. A second group of bHLH proteins contains an additional dimerization domain, the leucine zipper [1148], immediately C-terminal to the HLH. These proteins are commonly referred to as bHLHZ proteins. Members of a third group of HLH proteins lack a functional DNA-binding domain and act as negative regulators of bHLH proteins.