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Quiescent adult skeletal muscle stem cells (satellite cells) are the main players of myogenesis assuring the possibility of growth and regeneration of the muscle tissue throughout adult life. The environmental stimuli that activate satellite cells induce their proliferation, leading on one hand to self-renewal and maintenance of the muscle stem cell reservoir, and on the other hand to the production of progenitor cells that further proliferate, differentiate, and fuse to form new muscle fibers. Hence, satellite cells constitute a perfect system to study the transitions involved in stem cell differentiation. The multistep process of myogenesis is orchestrated by specific regulatory proteins, such as Pax3/Pax7 or members of the MyoD family of transcription factors. However, findings published over the past few years indicate that epigenetic mechanisms, such as covalent modification of histones, DNA methylation, or regulation of gene expression by microRNAs, also critically repress, maintain, or induce the muscle-specific transcriptional program during myogenesis. These studies have increased our understanding of how the information encoding the muscle lineage is molecularly controlled.