MyoD undergoes a distinct G2/M-specific regulation in muscle cells.
The transcription factors MyoD and Myf5 present distinct patterns of expression during cell cycle progression and development. In contrast to the mitosis-specific disappearance of Myf5, which requires a D-box-like motif overlapping the basic domain, here we describe a stable and inactive mitotic form of MyoD phosphorylated on its serine 5 and serine 200 residues by cyclin B-cdc2. In mitosis, these modifications are required for releasing MyoD from condensed chromosomes and inhibiting its DNA-binding and transcriptional activation ability. Then, nuclear MyoD regains instability in the beginning of G1 phase due to rapid dephosphorylation events. Moreover, a non-phosphorylable MyoD S5A/S200A is not excluded from condensed chromatin and alters mitotic progression with apparent abnormalities. Thus, the drop of MyoD below a threshold level and its displacement from the mitotic chromatin could present another window in the cell cycle for resetting the myogenic transcriptional program and to maintain the myogenic determination of the proliferating cells.
Batonnet-Pichon
Sabrina
S
Laboratoire de Génomique Fonctionnelle et Myogénèse, UMR 866 Différenciation, Cellulaire et Croissance, INRA UM II, Campus INRA/ENSA, 2 Place Pierre Viala, 34060, Montpellier, Cedex 1, France.
Tintignac
Lionel J
LJ
Castro
Anna
A
Sirri
Valentina
V
Leibovitch
Marie Pierre
MP
Lorca
Thierry
T
Leibovitch
Serge A
SA
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D002875:Chromosomes / Q000235:genetics / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D016195:G2 Phase; D051379:Mice; D008938:Mitosis; D032342:Muscle Cells / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism
D019926:Cyclin B; D017570:MyoD Protein; D025801:Ubiquitin; D012694:Serine; D016203:CDC2 Protein Kinase; D046988:Proteasome Endopeptidase Complex