microRNAs in skeletal muscle differentiation and disease

2012 ◽  
Vol 123 (11) ◽  
pp. 611-625 ◽  
Author(s):  
Katarzyna Goljanek-Whysall ◽  
Dylan Sweetman ◽  
Andrea E. Münsterberg
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
Muscle Development ◽  
Transcriptional Regulators ◽  
Skeletal Muscle Differentiation ◽  
Novel Therapies ◽  
Muscle Adaptation ◽  
Embryonic Muscle ◽  
Embryonic Muscle Development ◽  
Potential Therapeutic Intervention

miRNAs (microRNAs) are novel post-transcriptional regulators of gene expression. Several miRNAs, expressed exclusively in muscle, play important roles during muscle development, growth and regeneration; other ubiquitously expressed miRNAs are also essential for muscle function. In the present review, we outline the miRNAs involved in embryonic muscle development and those that have been found to be dysregulated in diseases associated with skeletal muscle or are changed during muscle adaptation. miRNAs are promising biomarkers and candidates for potential therapeutic intervention. We discuss the strategies that aim to develop novel therapies through modulating miRNA activity. In time, some of these approaches may become available to treat muscle-associated diseases.

scholarly journals The Landscape of Chromatin Accessibility in Skeletal Muscle During Embryonic Development in Pigs

2020 ◽  
Author(s):  
Jingwei Yue ◽  
Xinhua Hou ◽  
Xin Liu ◽  
Ligang Wang ◽  
Hongmei Gao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Embryonic Development ◽  
Muscle Development ◽  
Chromatin Accessibility ◽  
Regulatory Role ◽  
Rna Seq ◽  
Skeletal Muscle Development ◽  
Embryonic Muscle ◽  
Embryonic Muscle Development

Abstract Background: The development of skeletal muscle during the embryonic stage in pigs is precisely regulated by transcriptional regulation, which depends on chromatin accessibility. However, how chromatin accessibility plays a regulatory role during embryonic skeletal muscle development in pigs has not been reported. To gain insight into the landscape of chromatin accessibility and the associated genome-wide transcriptome during embryonic muscle development, we performed ATAC-seq and RNA-seq on skeletal muscle of pig embryos at 45, 70 and 100 days post coitus (dpc). Results: In total, 21638, 35447 and 60181 unique regions (or peaks) were found across 45 dpc (LW45), 70 dpc (LW70) and 100 dpc (LW100) embryos, respectively. More than 91% of peaks were annotated within -1 kb to 100 bp of transcription start sites (TSSs). First, widespread increases in specific accessible chromatin regions (ACRs) from 45 to 100 dpc embryos suggested that the regulatory mechanisms became increasingly complicated during embryonic development. Second, the findings of integrated ATAC-seq and RNA-seq analyses showed that not only the numbers but also the peak intensities of ACRs could control the expression of associated genes. Finally, motif screening of stage-specific ACRs revealed some transcription factors that regulated muscle development-related genes, such as MyoD, Mef2c, Mef2d and Pax7. Several potential transcriptional repressors, including E2F6, GRHL2, OTX2 and CTCF, were identified among those genes that exhibited different change trends between the ATAC-seq and RNA-seq data. Conclusions: This work indicates that chromatin accessibility plays an important regulatory role in the embryonic muscle development of pigs and regulates the temporal and spatial expression patterns of key genes in muscle development by influencing the binding of transcription factors. Our results contribute to a better understanding of the regulatory dynamics of genes involved in pig embryonic skeletal muscle development.

scholarly journals The landscape of chromatin accessibility in skeletal muscle during embryonic development in pigs

2021 ◽  
Author(s):  
Jingwei Yue ◽  
Xinhua Hou ◽  
Xin Liu ◽  
Ligang Wang ◽  
Hongmei Gao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Embryonic Development ◽  
Muscle Development ◽  
Expression Patterns ◽  
Chromatin Accessibility ◽  
Rna Seq ◽  
Transcription Start Sites ◽  
Embryonic Muscle ◽  
Embryonic Muscle Development

Abstract Background: The development of skeletal muscle during the embryonic stage in pigs is precisely regulated by transcriptional mechanisms, which depends on chromatin accessibility. However, the landscape of chromatin accessibility in skeletal muscle during embryonic development in pigs has not been reported. To gain insight into the landscape of chromatin accessibility and the associated genome-wide transcriptome during embryonic muscle development, we performed ATAC-seq and RNA-seq on skeletal muscle of pig embryos at 45, 70 and 100 days post coitus (dpc).Results: In total, 21638, 35447 and 60181 unique regions (or peaks) were found across 45 dpc (LW45), 70 dpc (LW70) and 100 dpc (LW100) embryos, respectively. More than 91% of peaks were annotated within -1 kb to 100 bp of transcription start sites (TSSs). First, widespread increases in specific accessible chromatin regions (ACRs) from 45 to 100 dpc embryos suggested that the regulatory mechanisms became increasingly complicated during embryonic development. Second, the findings of integrated ATAC-seq and RNA-seq analyses showed that not only the numbers but also the peak intensities of ACRs could control the expression of associated genes. Finally, motif screening of stage-specific ACRs revealed some transcription factors that regulated muscle development-related genes, such as MyoD, Mef2c, and Mef2d. Motif screening of DPI of common peaks detected that a potential transcriptional repressor, namely CTCF, was identified among those genes that exhibited different change trends between the ATAC-seq and RNA-seq data.Conclusions: This work indicates that chromatin accessibility plays an important regulatory role in the embryonic muscle development of pigs and regulates the temporal and spatial expression patterns of key genes in muscle development by influencing the binding of transcription factors. Our results contribute to a better understanding of the regulatory dynamics of genes involved in pig embryonic skeletal muscle development.

scholarly journals The landscape of chromatin accessibility in skeletal muscle during embryonic development in pigs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jingwei Yue ◽  
Xinhua Hou ◽  
Xin Liu ◽  
Ligang Wang ◽  
Hongmei Gao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Embryonic Development ◽  
Muscle Development ◽  
Chromatin Accessibility ◽  
Regulatory Role ◽  
Rna Seq ◽  
Skeletal Muscle Development ◽  
Embryonic Muscle ◽  
Embryonic Muscle Development

Abstract Background The development of skeletal muscle in pigs during the embryonic stage is precisely regulated by transcriptional mechanisms, which depend on chromatin accessibility. However, how chromatin accessibility plays a regulatory role during embryonic skeletal muscle development in pigs has not been reported. To gain insight into the landscape of chromatin accessibility and the associated genome-wide transcriptome during embryonic muscle development, we performed ATAC-seq and RNA-seq analyses of skeletal muscle from pig embryos at 45, 70 and 100 days post coitus (dpc). Results In total, 21,638, 35,447 and 60,181 unique regions (or peaks) were found across the embryos at 45 dpc (LW45), 70 dpc (LW70) and 100 dpc (LW100), respectively. More than 91% of the peaks were annotated within − 1 kb to 100 bp of transcription start sites (TSSs). First, widespread increases in specific accessible chromatin regions (ACRs) from embryos at 45 to 100 dpc suggested that the regulatory mechanisms became increasingly complicated during embryonic development. Second, the findings from integrated ATAC-seq and RNA-seq analyses showed that not only the numbers but also the intensities of ACRs could control the expression of associated genes. Moreover, the motif screening of stage-specific ACRs revealed some transcription factors that regulate muscle development-related genes, such as MyoG, Mef2c, and Mef2d. Several potential transcriptional repressors, including E2F6, OTX2 and CTCF, were identified among the genes that exhibited different regulation trends between the ATAC-seq and RNA-seq data. Conclusions This work indicates that chromatin accessibility plays an important regulatory role in the embryonic muscle development of pigs and regulates the temporal and spatial expression patterns of key genes in muscle development by influencing the binding of transcription factors. Our results contribute to a better understanding of the regulatory dynamics of genes involved in pig embryonic skeletal muscle development.

scholarly journals Genome-Wide Analysis of H3K27me3 in Porcine Embryonic Muscle Development

2021 ◽  
Vol 9 ◽  
Author(s):  
Baohua Tan ◽  
Sheng Wang ◽  
Shanshan Wang ◽  
Jiekang Zeng ◽  
Linjun Hong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Transcriptional Activation ◽  
Muscle Development ◽  
Global Scale ◽  
Genome Wide ◽  
H3k27me3 Level ◽  
Repressive Mark ◽  
Embryonic Muscle ◽  
Embryonic Muscle Development

The trimethylation of histone H3 lysine 27 (H3K27me3) is one of the most important chromatin modifications, which is generally presented as a repressive mark in various biological processes. However, the dynamic and global-scale distribution of H3K27me3 during porcine embryonic muscle development remains unclear. Here, our study provided a comprehensive genome-wide view of H3K27me3 and analyzed the matching transcriptome in the skeletal muscles on days 33, 65, and 90 post-coitus from Duroc fetuses. Transcriptome analysis identified 4,124 differentially expressed genes (DEGs) and revealed the key transcriptional properties in three stages. We found that the global H3K27me3 levels continually increased during embryonic development, and the H3K27me3 level was negatively correlated with gene expression. The loss of H3K27me3 in the promoter was associated with the transcriptional activation of 856 DEGs in various processes, including skeletal muscle development, calcium signaling, and multiple metabolic pathways. We also identified for the first time that H3K27me3 could enrich in the promoter of genes, such as DES, MYL1, TNNC1, and KLF5, to negatively regulate gene expression in porcine satellite cells (PSCs). The loss of H3K27me3 could promote muscle cell differentiation. Taken together, this study provided the first genome-wide landscape of H3K27me3 in porcine embryonic muscle development. It revealed the complex and broad function of H3K27me3 in the regulation of embryonic muscle development from skeletal muscle morphogenesis to myofiber maturation.

scholarly journals Evolutionarily conserved regulation of embryonic fast-twitch skeletal muscle differentiation by Pbx factors

2020 ◽  
Author(s):  
Gist H. Farr ◽  
Bingsi Li ◽  
Maurizio Risolino ◽  
Nathan M. Johnson ◽  
Zizhen Yao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Muscle Differentiation ◽  
Mouse Embryos ◽  
Fast Muscle ◽  
Fiber Types ◽  
Skeletal Muscle Differentiation ◽  
Homeodomain Proteins ◽  
Evolutionarily Conserved ◽  
Fast Twitch

SummaryVertebrate skeletal muscles are composed of both slow-twitch and fast-twitch fiber types. How the differentiation of distinct fiber types is activated during embryogenesis is not well characterized. Skeletal muscle differentiation is initiated by the activity of the myogenic basic helix-loop-helix (bHLH) transcription factors Myf5, Myod1, Myf6, and Myog. Myod1 functions as a muscle master regulatory factor and directly activates muscle differentiation genes, including those specific to both slow and fast muscle fibers. Our previous studies showed that Pbx TALE-class homeodomain proteins bind with Myod1 on the promoter of the zebrafish fast muscle gene mylpfa and are required for proper activation of mylpfa expression and the fast-twitch muscle-specific differentiation program in zebrafish embryos. Pbx proteins have also been shown to bind regulatory regions of muscle differentiation genes in mammalian muscle cells in culture. Here, we use new zebrafish mutant strains to confirm the essential roles of zebrafish Pbx factors in embryonic fast muscle differentiation. Furthermore, we examine the requirements for Pbx genes in mouse embryonic skeletal muscle differentiation, an area that has not been investigated in the mammalian embryo. Removing Pbx1 function from skeletal muscle in Myf5Cre/+;Pbx1fl/fl mouse embryos has minor effects on embryonic muscle development. However, concomitantly deleting Pbx2 function in Myf5Cre/+;Pbx1fl/fl;Pbx2-/- mouse embryos causes delayed activation and reduced expression of fast muscle differentiation genes. In the mouse, Pbx1/Pbx2-dependent fast muscle genes closely match those that have been previously shown to be dependent on murine Six1 and Six4. This work establishes evolutionarily conserved requirements for Pbx factors in embryonic fast muscle differentiation. Our studies are revealing how Pbx homeodomain proteins help direct specific cellular differentiation pathways.

The mutant not enough muscles (nem) reveals reduction of the Drosophila embryonic muscle pattern

1995 ◽  
Vol 108 (4) ◽  
pp. 1443-1454 ◽  
Author(s):  
S. Burchard ◽  
A. Paululat ◽  
U. Hinz ◽  
R. Renkawitz-Pohl
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Muscle Development ◽  
P Element ◽  
Dual Function ◽  
Methane Sulfonate ◽  
Visceral Mesoderm ◽  
Embryonic Muscle ◽  
Embryonic Muscle Development ◽  
Somatic Musculature

In a search for mutations affecting embryonic muscle development in Drosophila we identified a mutation caused by the insertion of a P-element, which we called not enough muscles (nem). The phenotype of the P-element mutation of the nem gene suggests that it may be required for the development of the somatic musculature and the chordotonal organs of the PNS, while it is not involved in the development of the visceral mesoderm and the dorsal vessel. Mutant embryos are characterized by partial absence of muscles, monitored by immunostainings with mesoderm-specific anti-beta 3 tubulin and anti-myosin heavy chain antibodies. Besides these muscle distortions, defects in the peripheral nervous system were found, indicating a dual function of the nem gene product. Ethyl methane sulfonate-induced alleles for the P-element mutation were created for a detailed analysis. One of these alleles is characterized by unfused myoblasts which express beta 3 tubulin and myosin heavy chain, indicating the state of cell differentiation.

scholarly journals Zfp422 promotes skeletal muscle differentiation by regulating EphA7 to induce appropriate myoblast apoptosis

2019 ◽  
Vol 27 (5) ◽  
pp. 1644-1659 ◽  
Author(s):  
Yaping Nie ◽  
Shufang Cai ◽  
Renqiang Yuan ◽  
Suying Ding ◽  
Xumeng Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Zinc Finger ◽  
Muscle Development ◽  
Zinc Finger Protein ◽  
Critical Role ◽  
Muscle Differentiation ◽  
C2c12 Cells ◽  
Myoblast Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Finger Protein

Abstract Zinc finger protein 422 (Zfp422) is a widely expressed zinc finger protein that serves as a transcriptional factor to regulate downstream gene expression, but until now, little is known about its roles in myogenesis. We found here that Zfp422 plays a critical role in skeletal muscle development and regeneration. It highly expresses in mouse skeletal muscle during embryonic development. Specific knockout of Zfp422 in skeletal muscle impaired embryonic muscle formation. Satellite cell-specific Zfp422 deletion severely inhibited muscle regeneration. Myoblast differentiation and myotube formation were suppressed in Zfp422-deleted C2C12 cells, isolated primary myoblasts, and satellite cells. Chromatin Immunoprecipitation Sequencing (ChIP-Seq) revealed that Zfp422 regulated ephrin type-A receptor 7 (EphA7) expression by binding an upstream 169-bp DNA sequence, which was proved to be an enhancer of EphA7. Knocking EphA7 down in C2C12 cells or deleting Zfp422 in myoblasts will inhibit cell apoptosis which is required for myoblast differentiation. These results indicate that Zfp422 is essential for skeletal muscle differentiation and fusion, through regulating EphA7 expression to maintain proper apoptosis.

scholarly journals Cytoskeleton and Adhesion in Myogenesis

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Manoel Luís Costa
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Muscle Function ◽  
Force Production ◽  
Structure And Function ◽  
Cytoskeletal Proteins ◽  
Skeletal Muscle Differentiation ◽  
And Function ◽  
Structural Adaptations

The function of muscle is to contract, which means to exert force on a substrate. The adaptations required for skeletal muscle differentiation, from a prototypic cell, involve specialization of housekeeping cytoskeletal contracting and supporting systems into crystalline arrays of proteins. Here I discuss the changes that all three cytoskeletal systems (microfilaments, intermediate filaments, and microtubules) undergo through myogenesis. I also discuss their interaction, through the membrane, to extracellular matrix and to other cells, where force will be exerted during contraction. The three cytoskeletal systems are necessary for the muscle cell and must exert complementary roles in the cell. Muscle is a responsive system, where structure and function are integrated: the structural adaptations it undergoes depend on force production. In this way, the muscle cytoskeleton is a portrait of its physiology. I review the cytoskeletal proteins and structures involved in muscle function and focus particularly on their role in myogenesis, the process by which this incredible muscle machine is made. Although the focus is on skeletal muscle, some of the discussion is applicable to cardiac and smooth muscle.

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