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HIF-1? Directly Controls WNT7A Expression During Myogenesis.

ABSTRACT: Herein we unveil that Hypoxia-inducible factor-1? (HIF-1?) directly regulates WNT7A expression during myogenesis. In fact, chromatin immunoprecipitation (ChiP) and site-directed mutagenesis experiments revealed two distinct hypoxia response elements (HREs) that are specific HIF-1? binding sites on the WNT7A promoter. Remarkably, a pharmacological activation of HIF-1? induced WNT7A expression and enhanced muscle differentiation. On the other hand, silencing of WNT7A using CRISPR/Cas9 genome editing blocked the effects of HIF-1? activation on myogenesis. Finally, treatment with prolyl hydroxylases (PHDs) inhibitors improved muscle regeneration in vitro and in vivo in a cardiotoxin (CTX)-induced muscle injury mouse model, paving the way for further studies to test its efficacy on acute and chronic muscular pathologies.

SUBMITTER: Cirillo F 

PROVIDER: S-EPMC7686515 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Herein we unveil that Hypoxia-inducible factor-1α (HIF-1α) directly regulates <i>WNT7A</i> expression during myogenesis. In fact, chromatin immunoprecipitation (ChiP) and site-directed mutagenesis experiments revealed two distinct hypoxia response elements (HREs) that are specific HIF-1α binding sites on the <i>WNT7A</i> promoter. Remarkably, a pharmacological activation of HIF-1α induced <i>WNT7A</i> expression and enhanced muscle differentiation. On the other hand, silencing of <i>WNT7A</i> us  ...[more]

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