title: Deconstruction of DNA methylation patterns during myogenesis reveals specific epigenetic events in the establishment of the skeletal muscle lineage.
abstract: The progressive restriction of differentiation potential from pluripotent embryonic stem cells (ESCs) to tissue-specific stem cells involves widespread epigenetic reprogramming, including modulation of DNA methylation patterns. Skeletal muscle stem cells are required for the growth, maintenance, and regeneration of skeletal muscle. To investigate the contribution of DNA methylation to the establishment of the myogenic program, we analyzed ESCs, skeletal muscle stem cells in proliferating (myoblasts) and differentiating conditions (myotubes), and mature myofibers. About 1.000 differentially methylated regions were identified during muscle-lineage determination and terminal differentiation, mainly located in gene bodies and intergenic regions. As a whole, myogenic stem cells showed a gain of DNA methylation, while muscle differentiation was accompanied by loss of DNA methylation in CpG-poor regions. Notably, the hypomethylated regions in myogenic stem cells were neighbored by enhancer-type chromatin, suggesting the involvement of DNA methylation in the regulation of cell-type specific enhancers. Interestingly, we demonstrated the hypomethylation of the muscle cell-identity Myf5 super-enhancer only in muscle cells. Furthermore, we observed that upstream stimulatory factor 1 binding to Myf5 super-enhancer occurs upon DNA demethylation in myogenic stem cells. Taken altogether, we characterized the unique DNA methylation signature of skeletal muscle stem cells and highlighted the importance of DNA methylation-mediated regulation of cell identity Myf5 super-enhancer during cellular differentiation.
authors: Institut de Medicina Predictiva i Personalitzada del Càncer (IMPPC).|Institut Germans Trias i Pujol (IGTP), Campus Can Ruti, 08916, Badalona, Spain.
authors: Elvira
authors: E
authors: Carrió
authors: Institut de Medicina Predictiva i Personalitzada del Càncer (IMPPC).|Institut Germans Trias i Pujol (IGTP), Campus Can Ruti, 08916, Badalona, Spain.
authors: Anna
authors: A
authors: Díez-Villanueva
authors: Institut de Medicina Predictiva i Personalitzada del Càncer (IMPPC).
authors: Sergi
authors: S
authors: Lois
authors: Institut de Medicina Predictiva i Personalitzada del Càncer (IMPPC).|Institut Germans Trias i Pujol (IGTP), Campus Can Ruti, 08916, Badalona, Spain.
authors: Izaskun
authors: I
authors: Mallona
authors: Institut de Medicina Predictiva i Personalitzada del Càncer (IMPPC).
authors: Ildefonso
authors: I
authors: Cases
authors: Institut de Medicina Predictiva i Personalitzada del Càncer (IMPPC).
authors: Marta
authors: M
authors: Forn
authors: Institut de Medicina Predictiva i Personalitzada del Càncer (IMPPC).|Institut Germans Trias i Pujol (IGTP), Campus Can Ruti, 08916, Badalona, Spain.
authors: Miguel A
authors: MA
authors: Peinado
authors: Institut de Medicina Predictiva i Personalitzada del Càncer (IMPPC).|Institut Germans Trias i Pujol (IGTP), Campus Can Ruti, 08916, Badalona, Spain.
authors: Mònica
authors: M
authors: Suelves
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D000066449:Human Embryonic Stem Cells / Q000378:metabolism; D006801:Humans; D024510:Muscle Development / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology*
chemical_list: D009124:Muscle Proteins
keywords: Cellular differentiation; DNA methylation; Myf5; Myogenesis; Stem cell; Super-enhancers