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Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex [ChIP-seq_H3k27ac]

ABSTRACT: Long noncoding RNAs play important roles in the spatial and temporal regulation of muscle development and regeneration. Nevertheless, the determination of their biological functions and mechanisms underlying muscle satellite cell differentiation remains challenging. Here, we identified a novel lncRNA named lncMREF as a specific positive regulator of muscle regeneration in mice, pigs and humans. Functional studies demonstrated that lncMREF is significantly upregulated in activated skeletal muscle satellite cells and promotes myogenic differentiation and muscle regeneration. Mechanistically, lncMREF interacts with Smarca5 to promote chromatin remodeling and accessibility when muscle satellite cells are activated, thereby facilitating genomic binding of p300/H3K27 to upregulate the expression of myogenic regulators, such as MyoD and cell differentiation. Our results unravel a new temporal-specific epigenetic regulation during muscle regeneration and reveal that lncMREF/Smarca5-mediated epigenetic programming is responsible for muscle satellite cell differentiation, which provides new insights into the regulatory mechanism of muscle regeneration in adult animals.

ORGANISM(S): Mus musculus

PROVIDER: GSE194027 | GEO | 2024/01/10

REPOSITORIES: GEO

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Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex [ATAC-seq]

Project description:Long noncoding RNAs play important roles in the spatial and temporal regulation of muscle development and regeneration. Nevertheless, the determination of their biological functions and mechanisms underlying muscle satellite cell differentiation remains challenging. Here, we identified a novel lncRNA named lncMREF as a specific positive regulator of muscle regeneration in mice, pigs and humans. Functional studies demonstrated that lncMREF is significantly upregulated in activated skeletal muscle satellite cells and promotes myogenic differentiation and muscle regeneration. Mechanistically, lncMREF interacts with Smarca5 to promote chromatin remodeling and accessibility when muscle satellite cells are activated, thereby facilitating genomic binding of p300/H3K27 to upregulate the expression of myogenic regulators, such as MyoD and cell differentiation. Our results unravel a new temporal-specific epigenetic regulation during muscle regeneration and reveal that lncMREF/Smarca5-mediated epigenetic programming is responsible for muscle satellite cell differentiation, which provides new insights into the regulatory mechanism of muscle regeneration in adult animals.

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Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex [ChIP-seq_p300]

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Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex [RNA-seq]

Project description:Here, we identified a novel lncRNA named lncMREF as a specific positive regulator of muscle regeneration in mice, pigs and humans. Functional studies demonstrated that lncMREF is significantly upregulated in activated skeletal muscle satellite cells and promotes myogenic differentiation and muscle regeneration. Mechanistically, lncMREF interacts with Smarca5 to promote chromatin remodeling and accessibility when muscle satellite cells are activated, thereby facilitating genomic binding of p300/H3K27 to upregulate the expression of myogenic regulators, such as MyoD and cell differentiation. Our results unravel a new temporal-specific epigenetic regulation during muscle regeneration and reveal that lncMREF/Smarca5-mediated epigenetic programming is responsible for muscle satellite cell differentiation, which provides new insights into the regulatory mechanism of muscle regeneration in adult animals.

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Project description:In response to skeletal muscle injury, adult myogenic stem cells, known as satellite cells, are activated and undergo proliferation and differentiation to regenerate new muscle fibers. The skeletal muscle-specific microRNA, miR-206, is up-regulated in satellite cells following muscle injury, but its role in muscle regeneration has not been defined. Here we show that skeletal muscle regeneration in response to cardiotoxin injury is impaired in mice lacking miR-206. Loss of miR-206 also accelerates and exacerbates the dystrophic phenotype of mdx mice, a model for Duchenne muscular dystrophy. MiR-206 promotes satellite cell differentiation and fusion to form multinucleated myofibers by suppressing a collection of negative regulators of myogenesis. Our findings reveal an essential role for miR-206 in satellite cell differentiation during skeletal muscle regeneration and as a modulator of Duchenne muscular dystrophy. total RNA obtained from TA muscle of mdx and 3 miR-206 KO; mdx mice at 3 months of age.

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Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex

Project description:Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex

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Human SMARCA5 interactome in transgenic SMARCA5 mouse model

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Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex [ATAC-seq]

Project description:Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex [ATAC-seq]

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Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex [RNA-seq]

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Project description:Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex [ChIP-seq_p300]

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