Dataset Information

The epigenetic regulation of embryonic myogenesis and adult muscle regeneration by histone methylation modification.

ABSTRACT: Skeletal muscle formation in vertebrates is derived from the paraxial mesoderm, which develops into myogenic precursor cells and finally differentiates into mature myofibers. This myogenic program involves temporal-spatial molecular events performed by transcription regulators (such as members of the Pax, MRFs and Six families) and signaling pathways (such as Wnts, BMP and Shh signaling). Epigenetic regulation, including histone post-translational modifications is crucial for controlling gene expression through recruitment of various chromatin-modifying enzymes that alter chromatin dynamics during myogenesis. The chromatin modifying enzymes are also recruited at regions of muscle gene regulation, coordinating transcription regulators to influence gene expression. In particular, the reversible methylation status of histone N-terminal tails provides the important regulatory mechanisms in either activation or repression of muscle genes. In this report, we review the recent literatures to deduce mechanisms underlying the epigenetic regulation of gene expression with a focus on histone methylation modification during embryo myogenesis and adult muscle regeneration. Recent results from different histone methylation/demethylation modifications have increased our understanding about the highly intricate layers of epigenetic regulations involved in myogenesis and cross-talk of histone enzymes with the muscle-specific transcriptional machinery.

SUBMITTER: Jin W

PROVIDER: S-EPMC5600456 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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The epigenetic regulation of embryonic myogenesis and adult muscle regeneration by histone methylation modification.

Jin Wei W Peng Jian J Jiang Siwen S

Biochemistry and biophysics reports 20160420

Skeletal muscle formation in vertebrates is derived from the paraxial mesoderm, which develops into myogenic precursor cells and finally differentiates into mature myofibers. This myogenic program involves temporal-spatial molecular events performed by transcription regulators (such as members of the Pax, MRFs and Six families) and signaling pathways (such as Wnts, BMP and Shh signaling). Epigenetic regulation, including histone post-translational modifications is crucial for controlling gene ex ...[more]

PMID: 28955879

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Project description:Skeletal muscle regeneration that follows acute injury is strongly influenced by interactions with immune cells that invade and proliferate in the damaged tissue. Discoveries over the past 20 years have identified many of the key mechanisms through which myeloid cells, especially macrophages, regulate muscle regeneration. In addition, lymphoid cells that include CD8+ T-cells and regulatory T-cells also significantly affect the course of muscle regeneration. During aging, the regenerative capacity of skeletal muscle declines, which can contribute to progressive loss of muscle mass and function. Those age-related reductions in muscle regeneration are accompanied by systemic, age-related changes in the immune system, that affect many of the myeloid and lymphoid cell populations that can influence muscle regeneration. In this review, we present recent discoveries that indicate that aging of the immune system contributes to the diminished regenerative capacity of aging muscle. Intrinsic, age-related changes in immune cells modify their expression of factors that affect the function of a population of muscle stem cells, called satellite cells, that are necessary for normal muscle regeneration. For example, age-related reductions in the expression of growth differentiation factor-3 (GDF3) or CXCL10 by macrophages negatively affect adult myogenesis, by disrupting regulatory interactions between macrophages and satellite cells. Those changes contribute to a reduction in the numbers and myogenic capacity of satellite cells in old muscle, which reduces their ability to restore damaged muscle. In addition, aging produces changes in the expression of molecules that regulate the inflammatory response to injured muscle, which also contributes to age-related defects in muscle regeneration. For example, age-related increases in the production of osteopontin by macrophages disrupts the normal inflammatory response to muscle injury, resulting in regenerative defects. These nascent findings represent the beginning of a newly-developing field of investigation into mechanisms through which aging of the immune system affects muscle regeneration.

Project description:Large fractions of eukaryotic genomes contain repetitive sequences of which the vast majority is derived from transposable elements (TEs). In order to inactivate those potentially harmful elements, host organisms silence TEs via methylation of transposon DNA and packaging into chromatin associated with repressive histone marks. The contribution of individual histone modifications in this process is not completely resolved. Therefore, we aimed to define the role of reversible histone acetylation, a modification commonly associated with transcriptional activity, in transcriptional regulation of murine TEs. We surveyed histone acetylation patterns and expression levels of ten different murine TEs in mouse fibroblasts with altered histone acetylation levels, which was achieved via chemical HDAC inhibition with trichostatin A (TSA), or genetic inactivation of the major deacetylase HDAC1. We found that one LTR retrotransposon family encompassing virus-like 30S elements (VL30) showed significant histone H3 hyperacetylation and strong transcriptional activation in response to TSA treatment. Analysis of VL30 transcripts revealed that increased VL30 transcription is due to enhanced expression of a limited number of genomic elements, with one locus being particularly responsive to HDAC inhibition. Importantly, transcriptional induction of VL30 was entirely dependent on the activation of MAP kinase pathways, resulting in serine 10 phosphorylation at histone H3. Stimulation of MAP kinase cascades together with HDAC inhibition led to simultaneous phosphorylation and acetylation (phosphoacetylation) of histone H3 at the VL30 regulatory region. The presence of the phosphoacetylation mark at VL30 LTRs was linked with full transcriptional activation of the mobile element. Our data indicate that the activity of different TEs is controlled by distinct chromatin modifications. We show that activation of a specific mobile element is linked to a dual epigenetic mark and propose a model whereby phosphoacetylation of histone H3 is crucial for full transcriptional activation of VL30 elements.

Project description:Rationale: The adult skeletal muscle can self-repair efficiently following mechanical or pathological damage due to its remarkable regenerative capacity. However, regulatory mechanisms underlying muscle regeneration are complicated and have not been fully elucidated. Alternative splicing (AS) is a major mechanism responsible for post-transcriptional regulation. Many aberrant AS events have been identified in patients with muscular dystrophy which is accompanied by abnormal muscle regeneration. However, little is known about the correlation between AS and muscle regeneration. It has been reported that RNA binding motif protein 24 (Rbm24), a tissue-specific splicing factor, is involved in embryo myogenesis while the role of Rbm24 in adult myogenesis (also called muscle regeneration) is poorly understood. Methods: To investigate the role of Rbm24 in adult skeletal muscle, we generated Rbm24 conditional knockout mice and satellite cell-specific knockout mice. Furthermore, a cardiotoxin (CTX)-induced injury model was utilized to assess the effects of Rbm24 on skeletal muscle regeneration. Genome-wide RNA-Seq was performed to identify the changes in AS following loss of Rbm24. Results: Rbm24 knockout mice displayed abnormal regeneration 4 months after tamoxifen treatment. Using RNA-Seq, we found that Rbm24 regulated a complex network of AS events involved in multiple biological processes, including myogenesis, muscle regeneration and muscle hypertrophy. Moreover, using a CTX-induced injury model, we showed that loss of Rbm24 in skeletal muscle resulted in myogenic fusion and differentiation defects and significantly delayed muscle regeneration. Furthermore, satellite cell-specific Rbm24 knockout mice recapitulated the defects in regeneration seen in the global Rbm24 knockout mice. Importantly, we demonstrated that Rbm24 regulated AS of Mef2d, Naca, Rock2 and Lrrfip1 which are essential for myogenic differentiation and muscle regeneration. Conclusions: The present study demonstrated that Rbm24 regulates dynamic changes in AS and is essential for adult skeletal muscle regeneration.

Dataset Information

The epigenetic regulation of embryonic myogenesis and adult muscle regeneration by histone methylation modification.

Publications

The epigenetic regulation of embryonic myogenesis and adult muscle regeneration by histone methylation modification.

Similar Datasets

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