© The Rockefeller University Press,
0021-9525/1998//1447 $5.00
The Journal of Cell Biology, Volume 142, Number 6,
, 1998 1447-1459
The Muscle Regulatory Factors MyoD and Myf-5 Undergo Distinct Cell Cycle–specific Expression in Muscle Cells
Magali Kitzmann*,
Gilles Carnac*,
Marie Vandromme*,
Michael Primig
,
Ned J.C. Lamb*, and
Anne Fernandez*
* Cell Biology Unit, Institut de Génétique Humaine, Unité Propre de Recherche 1142, Centre National de la Recherche Scientifique, 34396 Montpellier Cedex 5, France; and
Institut Pasteur, Department de Biologie Moleculaire, 75724 Paris Cedex 15, France
The muscle regulators MyoD and Myf-5 control cell cycle withdrawal and induction of differentiation in skeletal muscle cells. By immunofluorescence analysis, we show that MyoD and Myf-5 expression patterns become mutually exclusive when C2 cells are induced to differentiate with Myf-5 staining present in cells which fail to differentiate. Isolation of these undifferentiated cells reveals that upon serum stimulation they reenter the cell cycle, express MyoD and downregulate Myf-5. Similar regulations of MyoD and Myf-5 were observed using cultured primary myoblasts derived from satellite cells. To further analyze these regulations of MyoD and Myf-5 expression, we synchronized proliferating myoblasts. Analysis of MyoD and Myf-5 expression during cell cycle progression revealed distinct and contrasting profiles of expression. MyoD is absent in G0, peaks in mid-G1, falls to its minimum level at G1/S and reaugments from S to M. In contrast, Myf-5 protein is high in G0, decreases during G1 and reappears at the end of G1 to remain stable until mitosis. These data demonstrate that the two myogenic factors MyoD and Myf-5 undergo specific and distinct cell cycle–dependent regulation, thus establishing a correlation between the cell cycle–specific ratios of MyoD and Myf-5 and the capacity of cells to differentiate: (a) in G1, when cells express high levels of MyoD and enter differentiation; (b) in G0, when cells express high levels of Myf-5 and fail to differentiate.
Key Words: cell cycle MyoD Myf-5 muscle differentiation
Abbreviations used in this paper: BrdU, 5-bromodeoxyuridine; cdk, cyclin-dependent kinase; CKI, cyclin-dependent kinase inhibitor; HU, hydroxyurea; pRb, retinoblastoma protein.
The first two authors contributed equally to this work.

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