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

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

PROVIDER: PRJNA798762 | ENA |

REPOSITORIES: ENA

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

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 [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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Project description:Long noncoding RNAs (lncRNAs) 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 regeneration remains challenging. Here, we identified a lncRNA named lncMREF (lncRNA muscle regeneration enhancement factor) as a conserved positive regulator of muscle regeneration among mice, pigs and humans. Functional studies demonstrated that lncMREF, which is mainly expressed in differentiated muscle satellite cells, promotes myogenic differentiation and muscle regeneration. Mechanistically, lncMREF interacts with Smarca5 to promote chromatin accessibility when muscle satellite cells are activated and start to differentiate, thereby facilitating genomic binding of p300/CBP/H3K27ac to upregulate the expression of myogenic regulators, such as MyoD and cell differentiation. Our results unravel a novel temporal-specific epigenetic regulation during muscle regeneration and reveal that lncMREF/Smarca5-mediated epigenetic programming is responsible for muscle cell differentiation, which provides new insights into the regulatory mechanism of muscle regeneration.

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