Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Amino Acid Sequence
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Animals
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Basic Helix-Loop-Helix Transcription Factors
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Blood Vessels / cytology
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Blood Vessels / embryology
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Cell Differentiation / genetics
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Cell Differentiation / physiology*
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Cell Lineage
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Cell Transformation, Neoplastic / genetics
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Dimerization
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Drosophila Proteins / genetics
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Drosophila Proteins / physiology
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Drosophila melanogaster / embryology
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Drosophila melanogaster / genetics
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Drosophila melanogaster / physiology
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Embryonic and Fetal Development / genetics
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Embryonic and Fetal Development / physiology*
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Evolution, Molecular
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Gene Expression Regulation, Developmental / genetics
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Gene Expression Regulation, Developmental / physiology*
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Helix-Loop-Helix Motifs
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Humans
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Leukemia-Lymphoma, Adult T-Cell / genetics
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Leukemia-Lymphoma, Adult T-Cell / pathology
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Membrane Proteins / genetics
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Membrane Proteins / physiology
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Mesoderm / cytology
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Mice
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Mice, Knockout
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Molecular Sequence Data
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Morphogenesis / genetics
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Morphogenesis / physiology
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Multigene Family*
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Muscles / cytology
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Muscles / embryology
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Neovascularization, Physiologic / genetics
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Neovascularization, Physiologic / physiology
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology
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Nervous System / embryology
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Neurons / cytology
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Phylogeny
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Protein Structure, Tertiary
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Proteins / genetics
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Proteins / physiology*
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Receptors, Notch
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Repressor Proteins / genetics
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Repressor Proteins / physiology*
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Sequence Alignment
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Sequence Homology, Amino Acid
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Terminology as Topic
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Transcription Factors
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Transcription, Genetic
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Vertebrates / embryology
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Vertebrates / genetics
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Vertebrates / physiology*
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Xenopus Proteins*
Substances
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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Drosophila Proteins
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ESR-5 protein, Xenopus
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Membrane Proteins
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N protein, Drosophila
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Nerve Tissue Proteins
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Proteins
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Receptors, Notch
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Repressor Proteins
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Transcription Factors
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Xenopus Proteins
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hes7.2 protein, Xenopus