Genome-Wide Analysis of H3K27me3 in Porcine 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.

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Comparative Analysis of Skeletal Muscle DNA Methylation and Transcriptome of the Chicken Embryo at Different Developmental Stages

Frontiers in Physiology ◽

10.3389/fphys.2021.697121 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jinshan Ran ◽

Jingjing Li ◽

Lingqian Yin ◽

Donghao Zhang ◽

Chunlin Yu ◽

...

Keyword(s):

Skeletal Muscle ◽

Dna Methylation ◽

Cell Proliferation ◽

Satellite Cell ◽

Muscle Development ◽

Muscle Satellite Cell ◽

Genome Wide ◽

Embryonic Muscle ◽

Skeletal Muscle Satellite Cell ◽

Chicken Skeletal Muscle

DNA methylation is a key epigenetic mechanism involved in embryonic muscle development and plays an important role in early muscle development. In this study, we sought to investigate the effects of genome-wide DNA methylation by combining the expression profiles of the chicken embryonic muscle. Genome-wide DNA methylation maps and transcriptomes of muscle tissues collected from different embryonic development points (E7, E11, E17, and D1) were used for whole-genome bisulfite sequencing (WGBS) and RNA sequencing, respectively. We found that the differentially methylated genes (DMGs) were significantly associated with muscle organ development, regulation of skeletal muscle satellite cell proliferation, and actin filament depolymerization. Furthermore, genes TBX1, MEF2D, SPEG, CFL2, and TWF2 were strongly correlated with the methylation-caused expression switch. Therefore, we chose the CFL2 gene to explore its function in skeletal muscle satellite cells, and the in vitro experiments showed that CFL2 acts as a negative regulator of chicken skeletal muscle satellite cell proliferation and can induce cell apoptosis. These results provide valuable data for future genome and epigenome studies of chicken skeletal muscle and may help reveal the molecular mechanisms of potential economic traits.

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

10.21203/rs.3.rs-95713/v1 ◽

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.

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

10.21203/rs.3.rs-95713/v2 ◽

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.

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

Journal of Animal Science and Biotechnology ◽

10.1186/s40104-021-00577-z ◽

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.

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microRNAs in skeletal muscle differentiation and disease

Clinical Science ◽

10.1042/cs20110634 ◽

2012 ◽

Vol 123 (11) ◽

pp. 611-625 ◽

Cited By ~ 52

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.

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Genome-Wide Analysis of Circular RNAs Mediated ceRNA Regulation in Porcine Embryonic Muscle Development

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2019.00289 ◽

2019 ◽

Vol 7 ◽

Cited By ~ 5

Author(s):

Linjun Hong ◽

Ting Gu ◽

Yanjuan He ◽

Chen Zhou ◽

Qun Hu ◽

...

Keyword(s):

Muscle Development ◽

Circular Rnas ◽

Genome Wide Analysis ◽

Genome Wide ◽

Embryonic Muscle ◽

Embryonic Muscle Development

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Histone modifications and exercise adaptations

Journal of Applied Physiology ◽

10.1152/japplphysiol.00979.2010 ◽

2011 ◽

Vol 110 (1) ◽

pp. 258-263 ◽

Cited By ~ 65

Author(s):

Sean L. McGee ◽

Mark Hargreaves

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Transcriptional Activation ◽

Nuclear Export ◽

Muscle Development ◽

Regulation Of Gene Expression ◽

Spatial Association ◽

Energy Status ◽

Histone Proteins ◽

Muscle Plasticity

The spatial association between genomic DNA and histone proteins within chromatin plays a key role in the regulation of gene expression and is largely governed by post-translational modifications to histone proteins, particularly H3 and H4. These modifications include phosphorylation, acetylation, and mono-, di-, and tri-methylation, and while some are associated with transcriptional repression, acetylation of lysine residues within H3 generally correlates with transcriptional activation. Histone acetylation is regulated by the balance between the activities of histone acetyl transferase (HAT) and histone deacetylase (HDAC). In skeletal muscle, the class II HDACs 4, 5, 7, and 9 play a key role in muscle development and adaptation and have been implicated in exercise adaptations. As just one example, exercise results in the nuclear export of HDACs 4 and 5, secondary to their phosphorylation by CaMKII and AMPK, two kinases that are activated during exercise in response to changes in sarcoplasmic Ca2+ levels and energy status, in association with increased GLUT4 expression in human skeletal muscle. Unraveling the complexities of the so-called “histone code” before and after exercise is likely to lead to a greater understanding of the regulation of exercise/activity-induced alterations in skeletal muscle gene expression and reinforce the importance of skeletal muscle plasticity in health and disease.

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Transcriptome Analysis of Differentially Expressed mRNA Related to Pigeon Muscle Development

Animals ◽

10.3390/ani11082311 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2311

Author(s):

Hao Ding ◽

Yueyue Lin ◽

Tao Zhang ◽

Lan Chen ◽

Genxi Zhang ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Differentially Expressed Genes ◽

Growth And Development ◽

Muscle Development ◽

Expression Patterns ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Growth Stages ◽

Gene Expression And Regulation

The mechanisms behind the gene expression and regulation that modulate the development and growth of pigeon skeletal muscle remain largely unknown. In this study, we performed gene expression analysis on skeletal muscle samples at different developmental and growth stages using RNA sequencing (RNA−Seq). The differentially expressed genes (DEGs) were identified using edgeR software. Weighted gene co−expression network analysis (WGCNA) was used to identify the gene modules related to the growth and development of pigeon skeletal muscle based on DEGs. A total of 11,311 DEGs were identified. WGCNA aggregated 11,311 DEGs into 12 modules. Black and brown modules were significantly correlated with the 1st and 10th day of skeletal muscle growth, while turquoise and cyan modules were significantly correlated with the 8th and 13th days of skeletal muscle embryonic development. Four mRNA−mRNA regulatory networks corresponding to the four significant modules were constructed and visualised using Cytoscape software. Twenty candidate mRNAs were identified based on their connectivity degrees in the networks, including Abca8b, TCONS−00004461, VWF, OGDH, TGIF1, DKK3, Gfpt1 and RFC5, etc. A KEGG pathway enrichment analysis showed that many pathways were related to the growth and development of pigeon skeletal muscle, including PI3K/AKT/mTOR, AMPK, FAK, and thyroid hormone pathways. Five differentially expressed genes (LAST2, MYPN, DKK3, B4GALT6 and OGDH) in the network were selected, and their expression patterns were quantified by qRT−PCR. The results were consistent with our sequencing results. These findings could enhance our understanding of the gene expression and regulation in the development and growth of pigeon muscle.

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H3 K79 dimethylation marks developmental activation of the β-globin gene but is reduced upon LCR-mediated high-level transcription

Blood ◽

10.1182/blood-2007-12-128983 ◽

2008 ◽

Vol 112 (2) ◽

pp. 406-414 ◽

Cited By ~ 11

Author(s):

Tomoyuki Sawado ◽

Jessica Halow ◽

Hogune Im ◽

Tobias Ragoczy ◽

Emery H. Bresnick ◽

...

Keyword(s):

Gene Expression ◽

Transcriptional Activation ◽

Globin Gene ◽

Erythroid Differentiation ◽

Genome Wide ◽

Activation Of Transcription ◽

High Level ◽

The Relationship ◽

Mutant Genes ◽

Gene Expression Levels

Abstract Genome-wide analyses of the relationship between H3 K79 dimethylation and transcription have revealed contradictory results. To clarify this relationship at a single locus, we analyzed expression and H3 K79 modification levels of wild-type (WT) and transcriptionally impaired β-globin mutant genes during erythroid differentiation. Analysis of fractionated erythroid cells derived from WT/Δ locus control region (LCR) heterozygous mice reveals no significant H3 K79 dimethylation of the β-globin gene on either allele prior to activation of transcription. Upon transcriptional activation, H3 K79 di-methylation is observed along both WT and ΔLCR alleles, and both alleles are located in proximity to H3 K79 dimethylation nuclear foci. However, H3 K79 di-methylation is significantly increased along the ΔLCR allele compared with the WT allele. In addition, analysis of a partial LCR deletion mutant reveals that H3 K79 dimethylation is inversely correlated with β-globin gene expression levels. Thus, while our results support a link between H3 K79 dimethylation and gene expression, high levels of this mark are not essential for high level β-globin gene transcription. We propose that H3 K79 dimethylation is destabilized on a highly transcribed template.

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