Summary
The Wnt/β-Catenin pathway plays a key role in cell fate determination during development and in adult tissue regeneration by stem cells. These processes involve profound gene expression and epigenome remodeling and linking Wnt/β-Catenin signaling to chromatin modifications has been a challenge over the past decades. Functional studies of the histone demethylase KDM1a/LSD1 converge to indicate that this epigenetic regulator is a key regulator of cell fate (Wang et al., 2007), although the extracellular cues controlling LSD1 action remain largely unknown. Here we show that β-Catenin is a substrate of LSD1. Demethylation by LSD1 prevents β-Catenin degradation thereby increasing its nuclear levels. In muscle stem cells, β-Catenin and LSD1 are both recruited on the MyoD Core Enhancer to control MyoD expression and promote muscle stem cell commitment (Pan et al., 2015; Scionti et al., 2017). Moreover, a β-Catenin reporter construct shows that the involvement of LSD1 in β-Catenin regulation is not restricted to MyoD activation. Altogether, by inscribing them in the same molecular cascade linking extracellular factors to epigenetic modifications and gene expression, our results provide a rational explanation to the similarity of action of canonical Wnt signaling and LSD1 on cell fate.
Competing Interest Statement
The authors have declared no competing interest.
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