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A more recent version of this article appeared on June 1, 2007
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Submitted on September 27, 2006
Revised on February 6, 2007
Accepted on March 14, 2007
Cell Biology Unit, Institut de Génétique Humaine (Centre National de la Recherche Scientifique, Unité Propre de Recherche 1142), 34396 Montpellier Cedex 05, France
Monitoring Editor: J. Silvio Gutkind
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 (DRR), is essential for MyoD expression in post-natal muscle. This enhancer contains a functional divergent SRF-binding CArG element required for MyoD expression during myoblast growth and muscle regeneration in vivo. EMSA, ChIP and microinjection analyses show this element is a hybrid SRF- and MEF2 Binding: SMB sequence where MEF2 complexes can compete out binding of SRF at the onset of differentiation. As cells differentiate into post-mitotic myotubes, MyoD expression no longer requires SRF but 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.
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