Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins.
Members of the myocyte enhancer factor-2 (MEF2) family of MADS domain transcription factors cannot induce myogenesis in transfected fibroblasts, but when coexpressed with the myogenic basic-helix-loop-helix (bHLH) proteins MyoD or myogenin they dramatically increase the extent of myogenic conversion above that seen with either myogenic bHLH factor alone. This cooperativity required direct interactions between the DNA-binding domains of MEF2 and the myogenic bHLH factors, but only one of the factors needed a transactivation domain, and only one of the factors needed to be bound to DNA. These interactions allow either factor to activate transcription through the other's binding site and reveal a novel mechanism for indirect activation of gene expression via protein-protein interactions between the DNA-binding domains of heterologous classes of transcription factors.
Department of Biochemistry and Molecular Biology University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
J D
JD
Molkentin
B L
BL
Black
J F
JF
Martin
E N
EN
Olson
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics*; D005314:Embryonic and Fetal Development; D005347:Fibroblasts / Q000502:physiology; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D064326:MEF2 Transcription Factors; D051379:Mice; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology* / Q000196:embryology / Q000502:physiology; D017570:MyoD Protein / Q000235:genetics; D018006:Myogenic Regulatory Factors; D018008:Myogenin / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; D017570:MyoD Protein; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D014157:Transcription Factors; C503801:Myog protein, mouse