Acquisition of myogenic specificity by replacement of three amino acid residues from MyoD into E12.
The basic helix-loop-helix (bHLH) protein MyoD is a transcription factor that is important for the induction of the myogenic phenotype. The DNA binding basic region (13 amino acids) is necessary for recognition of the consensus MyoD binding site, for transcriptional activation, and for conversion of fibroblasts to muscle. In contrast, the non-tissue-specific bHLH protein E12 can bind to the MyoD binding site but does not induce myogenesis. Here, it is shown that only two amino acids in the MyoD basic region and a single amino acid from the junction, which separates the basic region and helix 1, are sufficient for myogenic specificity when substituted into the corresponding region of E12. These findings suggest that the recognition of particular determinants in the basic region is required for conversion of fibroblasts to muscle.
Davis
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RL
Howard Hughes Medical Institute Laboratory, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Weintraub
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H
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology; D005455:Fluorescent Antibody Technique; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009132:Muscles / Q000166:cytology*; D017570:MyoD Protein; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection
D015342:DNA Probes; D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D017570:MyoD Protein; D014157:Transcription Factors; D004247:DNA