The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation

Davis, Robert L.; Cheng, Pei-Feng; Lassar, Andrew B.; Weintraub, Harold

doi:10.1016/0092-8674(90)90088-v

Cited by 765Muscle Physiology and DisordersGenomics and Chromatin DynamicsDevelopmental Biology and Gene Regulation

The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation

Davis, Robert L., Cheng, Pei-Feng, Lassar, Andrew B., Weintraub, Harold·1990·Cell

DOI 10.1016/0092-8674(90)90088-v

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Abstract

A 60 amino acid domain of the myogenic determination gene MyoD is necessary and sufficient for sequence-specific DNA binding in vitro and myogenic conversion of transfected C3H10T1/2 cells. We show that a highly basic region, immediately upstream of the helix-loop-helix (HLH) oligomerization motif, is required for MyoD DNA binding in vitro. Replacing helix1, helix2, or the loop of MyoD with the analogous sequence of the Drosophila T4 achaete-scute protein (required for peripheral neurogenesis) has no substantial effect on DNA binding in vitro or muscle-specific gene activation in transfected C3H10T1/2 cells. However, replacing the basic region of MyoD with the analogous sequence of other HLH proteins (the immunoglobulin enhancer binding E12 protein or T4 achaete scute protein) allows DNA binding in vitro, yet abolishes muscle-specific gene activation. These findings suggest that a recognition code that determines muscle-specific gene activation lies within the MyoD basic region and that the capacity for specific DNA binding is insufficient to activate the muscle program.

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“Mutation analysis has shown that the amino acids A114, T115, and K124 of mouse MyoD1 are crucial for myogenic activity.”
From Evolutionary aspects of developmentally regulated helix-loop-helix transcription factors in striated muscle of jellyfish (2003) · cites this paper as Davis et al., 1990
Placing the corresponding amino acid residues from MyoD1 into its dimerization partner E-12 produces a protein that functions as a myogenic activator.
“Remarkably, placing the corresponding amino acid residues from MyoD1 into its dimerization partner E-12 produces a protein that functions as myogenic activator”
From Evolutionary aspects of developmentally regulated helix-loop-helix transcription factors in striated muscle of jellyfish (2003) · cites this paper as Davis et al., 1990
JellyD1 contains two of the crucial amino acids needed for myogenic activity.
“JellyD1 contains two of the crucial amino acids needed for myogenic activity”
From Evolutionary aspects of developmentally regulated helix-loop-helix transcription factors in striated muscle of jellyfish (2003) · cites this paper as Davis et al., 1990

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Self-citation

Authors: Davis, R. L., Cheng, P.-F., Lassar, A. B., & Weintraub, H.
Affiliations: University of Washington (US)
Fred Hutch Cancer Center (US)
ORCID: Davis, Robert L.
Lassar, Andrew B.
Venue: Cell
Publisher: Elsevier BV
Published: 1990-03
Volume: 60
Issue: 5
Pages: 733-746
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/0092-8674(90)90088-v
OpenAlex: W2078709292
Cited by: 765
References: 52
Citations by year: 2026: 2 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 7 · 2016: 9 · 2015: 5 · 2014: 5 · 2013: 8 · 2012: 12
FWCI: 45.35
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords: MyoD, DNA-binding domain, helix-loop-helix proteins, basic region, E12, C3H10T1/2 cells, sequence-specific DNA binding, transcriptional activation
MeSH terms: Amino Acid Sequence, Animals, Base Sequence, Cell Differentiation, Cells, Cultured, Chromosome Deletion, DNA, Enhancer Elements, Genetic, Gene Expression Regulation, Genes, Models, Molecular, Molecular Sequence Data, Muscle Proteins, Muscles, Protein Conformation, Transfection, Oligonucleotide Probes, Transcriptional Activation, MyoD Protein, Mice

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The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation

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