Identification of a new hybrid serum response factor and myocyte enhancer factor 2-binding element in MyoD enhancer required for MyoD expression during myogenesis.
MyoD is a critical myogenic factor induced rapidly upon activation of quiescent satellite cells, and required for their differentiation during muscle regeneration. One of the two enhancers of MyoD, the distal regulatory region, is essential for MyoD expression in postnatal muscle. This enhancer contains a functional divergent serum response factor (SRF)-binding CArG element required for MyoD expression during myoblast growth and muscle regeneration in vivo. Electrophoretic mobility shift assay, chromatin immunoprecipitation, and microinjection analyses show this element is a hybrid SRF- and MEF2 Binding (SMB) sequence where myocyte enhancer factor 2 (MEF2) complexes can compete out binding of SRF at the onset of differentiation. As cells differentiate into postmitotic myotubes, MyoD expression no longer requires SRF but instead MEF2 binding to this dual-specificity element. As such, the MyoD enhancer SMB element is the site for a molecular relay where MyoD expression is first initiated in activated satellite cells in an SRF-dependent manner and then increased and maintained by MEF2 binding in differentiated myotubes. Therefore, SMB is a DNA element with dual and stage-specific binding activity, which modulates the effects of regulatory proteins critical in controlling the balance between proliferation and differentiation.
L'honore
Aurore
A
Cell Biology Unit, Institut de Génétique Humaine, Centre National de la Recherche Scientifique, 34396 Montpellier Cedex 05, France.
Rana
Vanessa
V
Arsic
Nikola
N
Franckhauser
Celine
C
Lamb
Ned J
NJ
Fernandez
Anne
A
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D064326:MEF2 Transcription Factors; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D012038:Regeneration / Q000502:physiology; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*
D064326:MEF2 Transcription Factors; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018006:Myogenic Regulatory Factors; D009841:Oligonucleotides; D026362:Serum Response Factor