Activation of muscle-specific transcription by myogenic helix-loop-helix proteins.

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Abstract

Myogenin is a muscle-specific transcription factor that acts as a molecular switch to induce myogenesis. Myogenin shares homology with MyoD and other myogenic regulatory proteins within a basic region and helix-loop-helix (HLH) motif that mediate binding to a conserved DNA sequence (CANNTG) present in the regulatory regions of numerous muscle-specific genes. Binding of myogenin and other members of the MyoD family to DNA can be augmented upon heterodimerization with the widely expressed HLH protein E12. We have used the muscle creatine kinase (MCK) enhancer as a target to study the mechanism whereby myogenin activates muscle-specific transcription. Full activity of the MCK enhancer requires cooperative interactions between myogenin (or other myogenic HLH proteins that bind the same site) and a complex array of ubiquitous and cell type-specific nuclear factors. To define the domains of myogenin responsible for sequence-specific DNA binding, activation of muscle-specific transcription, and cooperativity with other transcription factors, we have generated an extensive series of mutants by site-directed mutagenesis and domain swapping. These mutants have revealed strong transcriptional activation domains in the N- and C-termini of myogenin that rely on a specific amino acid sequence within the DNA binding domain for activity. Myogenin's ability to induce muscle-specific transcription is subject to negative regulation by growth factor and oncogenic signals. Mechanisms through which growth signals may repress myogenin function are discussed.

Original languageEnglish (US)
Pages (from-to)331-341
Number of pages11
JournalSymposia of the Society for Experimental Biology
Volume46
StatePublished - 1992

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Myogenin
Muscles
Proteins
MM Form Creatine Kinase
Helix-Loop-Helix Motifs
Transcription Factors
Transcription Factor 3
Aptitude
Muscle Development
Conserved Sequence
Nucleic Acid Regulatory Sequences
DNA
Site-Directed Mutagenesis
Transcriptional Activation
Amino Acid Sequence
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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title = "Activation of muscle-specific transcription by myogenic helix-loop-helix proteins.",
abstract = "Myogenin is a muscle-specific transcription factor that acts as a molecular switch to induce myogenesis. Myogenin shares homology with MyoD and other myogenic regulatory proteins within a basic region and helix-loop-helix (HLH) motif that mediate binding to a conserved DNA sequence (CANNTG) present in the regulatory regions of numerous muscle-specific genes. Binding of myogenin and other members of the MyoD family to DNA can be augmented upon heterodimerization with the widely expressed HLH protein E12. We have used the muscle creatine kinase (MCK) enhancer as a target to study the mechanism whereby myogenin activates muscle-specific transcription. Full activity of the MCK enhancer requires cooperative interactions between myogenin (or other myogenic HLH proteins that bind the same site) and a complex array of ubiquitous and cell type-specific nuclear factors. To define the domains of myogenin responsible for sequence-specific DNA binding, activation of muscle-specific transcription, and cooperativity with other transcription factors, we have generated an extensive series of mutants by site-directed mutagenesis and domain swapping. These mutants have revealed strong transcriptional activation domains in the N- and C-termini of myogenin that rely on a specific amino acid sequence within the DNA binding domain for activity. Myogenin's ability to induce muscle-specific transcription is subject to negative regulation by growth factor and oncogenic signals. Mechanisms through which growth signals may repress myogenin function are discussed.",
author = "E. Olson",
year = "1992",
language = "English (US)",
volume = "46",
pages = "331--341",
journal = "Symposia of the Society for Experimental Biology",
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T1 - Activation of muscle-specific transcription by myogenic helix-loop-helix proteins.

AU - Olson, E.

PY - 1992

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N2 - Myogenin is a muscle-specific transcription factor that acts as a molecular switch to induce myogenesis. Myogenin shares homology with MyoD and other myogenic regulatory proteins within a basic region and helix-loop-helix (HLH) motif that mediate binding to a conserved DNA sequence (CANNTG) present in the regulatory regions of numerous muscle-specific genes. Binding of myogenin and other members of the MyoD family to DNA can be augmented upon heterodimerization with the widely expressed HLH protein E12. We have used the muscle creatine kinase (MCK) enhancer as a target to study the mechanism whereby myogenin activates muscle-specific transcription. Full activity of the MCK enhancer requires cooperative interactions between myogenin (or other myogenic HLH proteins that bind the same site) and a complex array of ubiquitous and cell type-specific nuclear factors. To define the domains of myogenin responsible for sequence-specific DNA binding, activation of muscle-specific transcription, and cooperativity with other transcription factors, we have generated an extensive series of mutants by site-directed mutagenesis and domain swapping. These mutants have revealed strong transcriptional activation domains in the N- and C-termini of myogenin that rely on a specific amino acid sequence within the DNA binding domain for activity. Myogenin's ability to induce muscle-specific transcription is subject to negative regulation by growth factor and oncogenic signals. Mechanisms through which growth signals may repress myogenin function are discussed.

AB - Myogenin is a muscle-specific transcription factor that acts as a molecular switch to induce myogenesis. Myogenin shares homology with MyoD and other myogenic regulatory proteins within a basic region and helix-loop-helix (HLH) motif that mediate binding to a conserved DNA sequence (CANNTG) present in the regulatory regions of numerous muscle-specific genes. Binding of myogenin and other members of the MyoD family to DNA can be augmented upon heterodimerization with the widely expressed HLH protein E12. We have used the muscle creatine kinase (MCK) enhancer as a target to study the mechanism whereby myogenin activates muscle-specific transcription. Full activity of the MCK enhancer requires cooperative interactions between myogenin (or other myogenic HLH proteins that bind the same site) and a complex array of ubiquitous and cell type-specific nuclear factors. To define the domains of myogenin responsible for sequence-specific DNA binding, activation of muscle-specific transcription, and cooperativity with other transcription factors, we have generated an extensive series of mutants by site-directed mutagenesis and domain swapping. These mutants have revealed strong transcriptional activation domains in the N- and C-termini of myogenin that rely on a specific amino acid sequence within the DNA binding domain for activity. Myogenin's ability to induce muscle-specific transcription is subject to negative regulation by growth factor and oncogenic signals. Mechanisms through which growth signals may repress myogenin function are discussed.

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