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The Pkm duet: Coordinating C2C12 myoblast proliferation and differentiation through Histone 3 phosphorylation and cBAF complex dynamics

GSE252751 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2024/05/01 Platform GPL23479
Summary
Pkm1 and Pkm2 kinases are expressed in differentiating skeletal myoblasts. Knockdown of Pkm1 or Pkm2, therefore, can affect myoblast differentiation, by two independent regulatory mechanisms involving histone phosphorylation and chromatin remodeling complexes. Pkm2 KD in C2C12 cells reduced the chromatin marks of phosphorylated H3-T6, H3-T11 and H3-T45 into several essential myogenic promoters, and consequently, prevented their expression. Also, the transcriptional analysis demonstrated that Pkm2 is required for the expression of the cBAF-specific subunits Dpf2 and Baf250a, which we have previously demonstrated are essential for myogenesis. In contrast, Pkm1 KD alters the localization of nuclear Dpf2 into the cytoplasm as well. Mechanistically, Pkm KD resulted in decreased binding of cBAF components to their myogenic target genes, which also suggested a positive regulation between the cBaf complex and the H3 phosphorylation marks.
Published in
Muscle-Specific Pyruvate Kinase Isoforms, Pkm1 and Pkm2, Regulate Mammalian SWI/SNF Proteins and Histone 3 Phosphorylation During Myoblast Differentiation
Olea-Flores M, Sharma T, Verdejo-Torres O et al. · bioRxiv : the preprint server for biology 2024 · PMID 38645038 · doi:10.1101/2024.04.10.588959
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Also filed as BioProject PRJNA1062386 and SRA study SRP482501. Searching any of these in the dataset finder brings you back here.

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