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PMID: 1648228 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mutagenesis of the myogenin basic region identifies an ancient protein motif critical for activation of myogenesis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 88 ·No. 13 ·1991-07-01 ·Pages 5675-9

Brennan TJ, Chakraborty T, Olson EN

Abstract

Myogenin is a muscle-specific nuclear factor that acts as a genetic switch to activate myogenesis. Myogenin, MyoD, and a growing number of proteins implicated in transcriptional control share sequence homology within a basic region and an adjacent helix-loop-helix motif. Here we identify by site-directed mutagenesis a 12-amino acid subdomain of the myogenin basic region essential for binding of DNA and activation of myogenesis. The basic region of the widely expressed helix-loop-helix protein E12 is conserved at 8 of these 12 residues and can mediate DNA binding when placed in myogenin, but it cannot activate myogenesis. Replacement of each of the four nonconserved residues of the myogenin basic region with the corresponding residues of E12 reveals two adjacent amino acids (Ala86-Thr) that can impart muscle specificity to the basic region. These residues are specific to, and conserved in, the basic regions of all known myogenic helix-loop-helix proteins from Drosophila to man, suggesting that they constitute part of an ancient protein motif required for activation of the myogenic program.

MeSH Terms
Amino Acid Sequence Animals Binding, Competitive Cell Differentiation DNA Mutational Analysis DNA-Binding Proteins/chemistry,genetics Gene Expression Regulation Mice Molecular Sequence Data Muscle Proteins/chemistry,genetics Muscles/cytology,physiology Myogenin Structure-Activity Relationship Transcription, Genetic
Chemicals
DNA-Binding Proteins Muscle Proteins Myog protein, mouse Myogenin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Brennan T J
Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston 77074.
Chakraborty T
Olson E N
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.88.13.5675
Published
1991-07-01
Pages
5675-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC51940
Subset
IM
Grants
PHS HHS · 183315 · United States
External Links
PubMed source DOI: 10.1073/pnas.88.13.5675 PMC Full Text View journal details
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