Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Influences cell fate decisions in the embryo by sequestering and blocking the activity of the bHLH transcription factors that control these decisions. Inhibits the binding of myogenic bHLH-containing complexes to E-box DNA, thereby preventing activation of muscle-specific target genes. Also inhibits the activity of neurogenic factor neurod1/neuroD. Plays a role in cell cycle progression and survival of neural crest progenitors; binding to either hes4-B/hairy2b or stat3 blocks the formation of transcription factor complexes and the repressor function of hes4-B/hairy2B, to allow neural crest progenitors to differentiate. May play a role in the regulation of the circadian rhythm. Homodimer (By similarity). Heterodimer with other HLH proteins. Interacts (via HLH domain) with the bHLH protein hes4/hairy2 (via Orange domain). Interacts with stat3. At gastrula stage, expressed in all three germ layers, but becomes localized to discrete domains of the developing nervous system during neurulation, including the anterior neural plate, cement gland, eye anlagen, otic placode and both cranial and trunk premigratory and early migratory neural crest cells. Also expressed in the most dorsal and ventral portions of the myotome, the developing heart and anterior blood islets, and in the tail fin mesenchyme. Expressed at a low level in limbs, with expression decreasing as limbs develop, but expressed at a high level in blastemas (regenerated limbs), where expression is localized to both the blastermal epidermis and mesenchyme. Widely expressed in adults including the liver and heart. Expressed both maternally and zygotically. Expressed at a low level in fertilized eggs and cleaving embryos. Zygotic expression begins after the midblastula transition (MBT) with expression levels rising during gastrulation, and remaining constant throughout neurulation and premetamorphic development. Also expressed in adults. By bmp and notch signaling, and in response to signaling events of early neural crest induction. Repressed by hes4/hairy2 in a DNA-binding dependent manner through repression of bmp4 transcription, but up-regulated by hes4/hairy2 acting via delta1 activation. By myc.