Estrogen receptor regulates MyoD gene expression by preventing AP-1-mediated repression.
Cell growth and differentiation are opposite events in the myogenic lineage. Growth factors block the muscle differentiation program by inducing the expression of transcription factors that negatively regulate the expression of muscle regulatory genes like MyoD. In contrast, extracellular clues that induce cell cycle arrest promote MyoD expression and muscle differentiation. Thus, the regulation of MyoD expression is critical for muscle differentiation. Here we show that estrogen induces MyoD expression in mouse skeletal muscle in vivo and in dividing myoblasts in vitro by relieving the MyoD promoter from AP-1 negative regulation through a mechanism involving estrogen receptor/AP-1 protein-protein interactions but independent of the estrogen receptor DNA binding activity.
Pedraza-Alva
G
G
Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62250, Mexico. gustavo@ibt.unam.mx
Zingg
J M
JM
Donda
A
A
Pérez-Martínez
L
L
D000818:Animals; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005786:Gene Expression Regulation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D024510:Muscle Development / Q000235:genetics*; D017570:MyoD Protein / Q000235:genetics*; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D004967:Estrogens; D017570:MyoD Protein; D016760:Proto-Oncogene Proteins c-fos; D011960:Receptors, Estrogen; D018808:Transcription Factor AP-1; D048031:JNK Mitogen-Activated Protein Kinases