UTX in muscle regeneration — the right dose and the right time
Ling Liu, Thomas A. Rando
Ling Liu, Thomas A. Rando
Published April 1, 2016; First published March 21, 2016
Citation Information: J Clin Invest. 2016;126(4):1233-1235. https://doi.org/10.1172/JCI86798.
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Commentary

UTX in muscle regeneration — the right dose and the right time

Abstract

Precise epigenetic modifications in stem cells control developmental programs and cell fate decisions. In particular, the addition or removal of trimethylation of histone 3 lysine 27 (H3K27me3) at lineage-specific genes has been linked to the repression of gene expression, and a precise balance of methyltransferases and demethylases within cells determines H3K27me3 levels. The demethylase UTX is essential for development and tissue homeostasis; however, a role for UTX in stem cell–mediated tissue regeneration is unknown. In this issue of the JCI, Dilworth and colleagues reveal that UTX and its demethylase activity are required in the muscle stem cell lineage for muscle regeneration in response to injury. Specifically, UTX mediates the removal of H3K27me3 in the promoter of the transcription factor myogenin, which regulates myogenic differentiation. The results of this study provide important insight into the contribution of epigenetic regulation in stem cell–mediated regeneration of adult tissues.

Authors

Ling Liu, Thomas A. Rando

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Figure 1

Activation and differentiation of satellite cells require precise temporal expression of linage-specific transcription factors.

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Activation and differentiation of satellite cells require precise tempor...
Quiescent satellite cells (QSCs), marked by high levels of the transcription factor PAX7, begin to proliferate in response to muscle damage as the result of injury or disease. The myogenic regulatory factor MyoD drives differentiation of activated satellite cells (ASCs) toward the myogenic lineage. In these committed myocytes, myogenin upregulation promotes differentiation and formation of new muscle fibers. In this issue, Faralli et al. reveal that the demethylase UTX is required for the differentiation of satellite cell progeny and mediates removal of the repressive H3K27me3 mark at the myogenin promoter (6).