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Malat1 interacts with Suv39h1 to regulate MyoD transcriptional activity and is down-regulated by miR-181 binding during myogenic differentiation and muscle regeneration

ABSTRACT: As one of the most abundant lncRNAs in various cell types the exact cellular function of Malat1 is a matter of intense investigation. In this study we characterized the function of Malat1 in skeletal muscle cells and muscle regeneration. Utilizing both cell culture and knock-out mouse, our findings demonstrate that Malat1 plays a role in regulating gene expression during myogenic differentiation of myoblast cells. Specifically, we found that knock-down of Malat1 accelerated the myogenic differentiation in cultured cells. Consistently in vivo Malat1 knock-out mouse displayed enhanced muscle regeneration after injury and deletion of Malat1 in dystrophic Mdx mouse also improved the muscle regeneration. Mechanistically, we showed that in the proliferating myoblasts, Malat1 recruits Suv39h1 to MyoD binding loci, causing trimethylation of histone 3 lysine 9 (H3K9me3) which suppresses the target gene expression. Upon differentiation, miR-181a expression increases and targets the nuclear Malat1 transcripts for degradation through Ago2 dependent nRISC machinery; the Malat1 decrease subsequently leads to the destabilization of Suv39h1/HP1β/HDAC1 repressive complex and displacement by a Set7 containing activating complex, which allows MyoD trans-activation to occur. Together our findings identify a regulatory axis of miR-181a-Malat1-MyoD/Suv39h1 in myogenesis and uncover a previously unknown molecular mechanism of Malat1 action in gene regulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE87569 | GEO | 2017/04/14

SECONDARY ACCESSION(S): PRJNA345206

REPOSITORIES: GEO

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