A number of eukaryotic proteins, which probably are sequence specific DNA-binding proteins that act as transcription factors, share a conserved domainof 40 to 50 amino acid residues. It has been proposed that this domain isformed of two amphipathic helices joined by a variable length linker regionthat could form a loop. This 'helix-loop-helix' (HLH) domain mediates proteindimerization and has been found in the proteins listed below. Mostof these proteins have an extra basic region of about 15 amino acid residuesthat is adjacent to the HLH domain and specifically binds to DNA. They arerefered as basic helix-loop-helix proteins (bHLH), and are classified in twogroups: class A (ubiquitous) and class B (tissue-specific). Members of thebHLH family bind variations on the core sequence 'CANNTG', also refered to asthe E-box motif. The homo- or heterodimerization mediated by the HLH domain isindependent of, but necessary for DNA binding, as two basic regions arerequired for DNA binding activity. The HLH proteins lacking the basic domain(Emc, Id) function as negative regulators, since they form heterodimers, butfail to bind DNA. The hairy-related proteins (hairy, E(spl), deadpan) alsorepress transcription although they can bind DNA. The proteins of thissubfamily act together with co-repressor proteins, like groucho, through theirC-terminal motif WRPW.