title: Acetylation is important for MyoD function in adult mice.
abstract: Acetylation is a post-translational modification that influences the activity of numerous proteins in vitro. Among them, the myogenic transcription factor MyoD shows an increased transcriptional activity in vitro when acetylated on two lysines (K): lysines 99 and 102. Here, we have investigated the biological relevance of this acetylation in vivo. Using specific antibodies, we show that endogenous MyoD is acetylated on lysines 99 and 102 in myoblasts. Moreover, we show the functional importance of acetylation in live animals by using a mutant of MyoD in which lysines 99 and 102 were replaced by arginines (R). Knock-in embryos homozygous for the MyoD(R99,102) allele expressed slightly reduced levels of MyoD but developed normally. However, the knock-in homozygous adult mice showed a phenotype that was almost identical to that of MyoD-knockout animals, including delayed muscle regeneration in vivo and an increased number of myoblasts but with reduced differentiation potential in vitro. Together, these results show the importance of MyoD acetylation for adult myogenesis.
authors.affiliation: Laboratoire Epigénétique et cancer, CNRS FRE 2944, Institut André Lwoff, 7 rue Guy Moquet, 94801 Villejuif, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Duquet
authors.forename: Anna
authors.initials: A
authors.lastname: Polesskaya
authors.forename: Sylvain
authors.initials: S
authors.lastname: Cuvellier
authors.forename: Slimane
authors.initials: S
authors.lastname: Ait-Si-Ali
authors.forename: Patrick
authors.initials: P
authors.lastname: Héry
authors.forename: Linda L
authors.initials: LL
authors.lastname: Pritchard
authors.forename: Matthieu
authors.initials: M
authors.lastname: Gerard
authors.forename: Annick
authors.initials: A
authors.lastname: Harel-Bellan
mesh_terms: D000107:Acetylation; D000483:Alleles; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000378:metabolism*; D006720:Homozygote; D008239:Lysine / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000196:embryology / Q000378:metabolism / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D032446:Myoblasts / Q000378:metabolism*; D010641:Phenotype; D014162:Transfection
chemical_list: D017570:MyoD Protein; D008239:Lysine