Vertebrate hairy and Enhancer of split related proteins: transcriptional repressors regulating cellular differentiation and embryonic patterning.
The basic-helix-loop-helix (bHLH) proteins are a superfamily of DNA-binding transcription factors that regulate numerous biological processes in both invertebrates and vertebrates. One family of bHLH transcriptional repressors is related to the Drosophila hairy and Enhancer-of-split proteins. These repressors contain a tandem arrangement of the bHLH domain and an adjacent sequence known as the Orange domain, so we refer to these proteins as bHLH-Orange or bHLH-O proteins. Phylogenetic analysis reveals the existence of four bHLH-O subfamilies, with distinct, evolutionarily conserved features. A principal function of bHLH-O proteins is to bind to specific DNA sequences and recruit transcriptional corepressors to inhibit target gene expression. However, it is likely that bHLH-O proteins repress transcription by additional mechanisms as well. Many vertebrate bHLH-O proteins are effectors of the Notch signaling pathway, and bHLH-O proteins are involved in regulating neurogenesis, vasculogenesis, mesoderm segmentation, myogenesis, and T lymphocyte development. In this review, we discuss mechanisms of action and biological roles for the vertebrate bHLH-O proteins, as well as some of the unresolved questions about the functions and regulation of these proteins during development and in human disease.
Davis
R L
RL
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Turner
D L
DL
D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D019281:Dimerization; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology*; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D005810:Multigene Family; D009132:Muscles / Q000166:cytology / Q000196:embryology; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D009420:Nervous System / Q000196:embryology; D009474:Neurons / Q000166:cytology; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D009626:Terminology as Topic; D014157:Transcription Factors; D014158:Transcription, Genetic; D014714:Vertebrates / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D029867:Xenopus Proteins
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; C120192:ESR-5 protein, Xenopus; C497759:N protein, Drosophila; C120191:hes7.2 protein, Xenopus