UTX mediates demethylation of H3K27me3 at muscle-specific genes during myogenesis.

Polycomb (PcG) and Trithorax (TrxG) group proteins act antagonistically to establish tissue-specific patterns of gene expression. The PcG protein Ezh2 facilitates repression by catalysing histone H3-Lys27 trimethylation (H3K27me3). For expression, H3K27me3 marks are removed and replaced by TrxG protein catalysed histone H3-Lys4 trimethylation (H3K4me3). Although H3K27 demethylases have been identified, the mechanism by which these enzymes are targeted to specific genomic regions to remove H3K27me3 marks has not been established. Here, we demonstrate a two-step mechanism for UTX-mediated demethylation at muscle-specific genes during myogenesis. Although the transactivator Six4 initially recruits UTX to the regulatory region of muscle genes, the resulting loss of H3K27me3 marks is limited to the region upstream of the transcriptional start site. Removal of the repressive H3K27me3 mark within the coding region then requires RNA Polymerase II (Pol II) elongation. Interestingly, blocking Pol II elongation on transcribed genes leads to increased H3K27me3 within the coding region, and formation of bivalent (H3K27me3/H3K4me3) chromatin domains. Thus, removal of repressive H3K27me3 marks by UTX occurs through targeted recruitment followed by spreading across the gene.

Noncoding RNAs as epigenetic mediators of skeletal muscle regeneration.

Skeletal muscle regeneration is a well-characterized biological process in which resident adult stem cells must undertake a series of cell-fate decisions to ensure efficient repair of the damaged muscle fibers while also maintaining the stem cell niche. Satellite cells, the main stem cell contributing to the repaired muscle fiber, are maintained in a quiescent state in healthy muscle. Upon injury, the satellite cells become activated, and proliferate to expand the muscle progenitor cell population before returning to the quiescent state or differentiating to become myofibers. Importantly, the determination of cell fate is controlled at the epigenetic level in response to environmental cues. In this review, we discuss our current understanding of the role played by noncoding RNAs (both miRNAs and long-noncoding RNAs) in the epigenetic control of muscle regeneration.