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Genomic-wide transcriptional profiling in primary myoblasts reveals Runx1-regulated genes in muscle regeneration.

Umansky KB, Feldmesser E, Groner Y - Genom Data (2015)

Bottom Line: In response to muscle damage the muscle adult stem cells are activated and differentiate into myoblasts that regenerate the damaged tissue.We employed Runx1-dependent gene expression, Chromatin Immunoprecipitation sequencing (ChIP-seq), Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) and histone H3K4me1/H3K27ac modification analyses to identify a subset of Runx1-regulated genes that are co-occupied by the TFs MyoD and c-Jun and are involved in muscle regeneration (Umansky et al.).The data is available at the GEO database under the superseries accession number GSE56131.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.

ABSTRACT
In response to muscle damage the muscle adult stem cells are activated and differentiate into myoblasts that regenerate the damaged tissue. We have recently showed that following myopathic damage the level of the Runx1 transcription factor (TF) is elevated and that during muscle regeneration this TF regulates the balance between myoblast proliferation and differentiation (Umansky et al.). We employed Runx1-dependent gene expression, Chromatin Immunoprecipitation sequencing (ChIP-seq), Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) and histone H3K4me1/H3K27ac modification analyses to identify a subset of Runx1-regulated genes that are co-occupied by the TFs MyoD and c-Jun and are involved in muscle regeneration (Umansky et al.). The data is available at the GEO database under the superseries accession number GSE56131.

No MeSH data available.


Related in: MedlinePlus

Correlation with previously-acquired data sets.(A, B) GSEA analysis of genes bound by all three TFs in comparison to Runx1-responsive genes in proliferating PMs (A) or gene expression data of WT myoblasts vs. differentiated myotubes (B). (C) The Runx1- and RMJ-bound loci in PM ChIP-seq were compared to published C2C12 cell line derived MyoD bound “Super enhancers” [16] loci. Percent overlapping loci of the relevant dataset are presented. C2C12 MyoD bound “Super-enhancers” compared to Runx1 and RMJ ChIP-seq. Overlap presented as percent of Super-enhancers.
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f0010: Correlation with previously-acquired data sets.(A, B) GSEA analysis of genes bound by all three TFs in comparison to Runx1-responsive genes in proliferating PMs (A) or gene expression data of WT myoblasts vs. differentiated myotubes (B). (C) The Runx1- and RMJ-bound loci in PM ChIP-seq were compared to published C2C12 cell line derived MyoD bound “Super enhancers” [16] loci. Percent overlapping loci of the relevant dataset are presented. C2C12 MyoD bound “Super-enhancers” compared to Runx1 and RMJ ChIP-seq. Overlap presented as percent of Super-enhancers.

Mentions: Skeletal muscle is a highly regenerative tissue. Upon muscle injury, the adult stem cells the satellite cells (SCs) are activated and differentiate and fuse to create myofibers that regenerate the tissue. While not expressed in healthy muscle tissue, expression of TF Runx1 significantly increases in response to various types of muscle damage including neuropathic damage [12], [13] and myopathic damage [1]. Specifically, we have recently shown that Runx1 prevents premature differentiation of SC-derived myoblasts during muscle regeneration [1]. In the myoblastic cell line C2C12 Runx1 was co-bound with the major myogenic factor, MyoD [14]. Using in vivo loss- and gain-of-function models and genome-wide transcriptional analyses we identify a subset of Runx1-regulateed genes that participate in muscle regeneration. Significantly, Runx1 transcriptome and ChIP-seq analysis show good correlation (Fig. 2A). Our ChIP-seq data also showed correlation with myoblast-specific transcriptional-profiling data. For example, we found that the proximity of myoblast-specific expressed genes [15] was highly enriched for co-binding of Runx1, MyoD and c-Jun (RMJ) (Fig. 2B). In addition, analysis of myoblast-specific Super-enhancers [16], revealed a strong overlap with our ChIP-seq data in sites regulating myoblast fate (Fig. 2C). Interestingly, Runx1 is involved in cell fate decision of additional adult stem cells populations, including hair follicle stem cells [17], and differentiation of mesenchymal stem cells into myofibroblasts [18]. It is conceivable that common transcription regulatory mechanisms are shared by the three systems. In summary, our data suggests that Runx1 regulates the core transcriptional program that determines myoblastic cell fate and facilitates muscle regeneration by preventing premature differentiation of proliferating myoblasts. The comprehensive data set provides a useful recourse for deciphering the molecular mechanisms underlying muscle regeneration.


Genomic-wide transcriptional profiling in primary myoblasts reveals Runx1-regulated genes in muscle regeneration.

Umansky KB, Feldmesser E, Groner Y - Genom Data (2015)

Correlation with previously-acquired data sets.(A, B) GSEA analysis of genes bound by all three TFs in comparison to Runx1-responsive genes in proliferating PMs (A) or gene expression data of WT myoblasts vs. differentiated myotubes (B). (C) The Runx1- and RMJ-bound loci in PM ChIP-seq were compared to published C2C12 cell line derived MyoD bound “Super enhancers” [16] loci. Percent overlapping loci of the relevant dataset are presented. C2C12 MyoD bound “Super-enhancers” compared to Runx1 and RMJ ChIP-seq. Overlap presented as percent of Super-enhancers.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664707&req=5

f0010: Correlation with previously-acquired data sets.(A, B) GSEA analysis of genes bound by all three TFs in comparison to Runx1-responsive genes in proliferating PMs (A) or gene expression data of WT myoblasts vs. differentiated myotubes (B). (C) The Runx1- and RMJ-bound loci in PM ChIP-seq were compared to published C2C12 cell line derived MyoD bound “Super enhancers” [16] loci. Percent overlapping loci of the relevant dataset are presented. C2C12 MyoD bound “Super-enhancers” compared to Runx1 and RMJ ChIP-seq. Overlap presented as percent of Super-enhancers.
Mentions: Skeletal muscle is a highly regenerative tissue. Upon muscle injury, the adult stem cells the satellite cells (SCs) are activated and differentiate and fuse to create myofibers that regenerate the tissue. While not expressed in healthy muscle tissue, expression of TF Runx1 significantly increases in response to various types of muscle damage including neuropathic damage [12], [13] and myopathic damage [1]. Specifically, we have recently shown that Runx1 prevents premature differentiation of SC-derived myoblasts during muscle regeneration [1]. In the myoblastic cell line C2C12 Runx1 was co-bound with the major myogenic factor, MyoD [14]. Using in vivo loss- and gain-of-function models and genome-wide transcriptional analyses we identify a subset of Runx1-regulateed genes that participate in muscle regeneration. Significantly, Runx1 transcriptome and ChIP-seq analysis show good correlation (Fig. 2A). Our ChIP-seq data also showed correlation with myoblast-specific transcriptional-profiling data. For example, we found that the proximity of myoblast-specific expressed genes [15] was highly enriched for co-binding of Runx1, MyoD and c-Jun (RMJ) (Fig. 2B). In addition, analysis of myoblast-specific Super-enhancers [16], revealed a strong overlap with our ChIP-seq data in sites regulating myoblast fate (Fig. 2C). Interestingly, Runx1 is involved in cell fate decision of additional adult stem cells populations, including hair follicle stem cells [17], and differentiation of mesenchymal stem cells into myofibroblasts [18]. It is conceivable that common transcription regulatory mechanisms are shared by the three systems. In summary, our data suggests that Runx1 regulates the core transcriptional program that determines myoblastic cell fate and facilitates muscle regeneration by preventing premature differentiation of proliferating myoblasts. The comprehensive data set provides a useful recourse for deciphering the molecular mechanisms underlying muscle regeneration.

Bottom Line: In response to muscle damage the muscle adult stem cells are activated and differentiate into myoblasts that regenerate the damaged tissue.We employed Runx1-dependent gene expression, Chromatin Immunoprecipitation sequencing (ChIP-seq), Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) and histone H3K4me1/H3K27ac modification analyses to identify a subset of Runx1-regulated genes that are co-occupied by the TFs MyoD and c-Jun and are involved in muscle regeneration (Umansky et al.).The data is available at the GEO database under the superseries accession number GSE56131.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.

ABSTRACT
In response to muscle damage the muscle adult stem cells are activated and differentiate into myoblasts that regenerate the damaged tissue. We have recently showed that following myopathic damage the level of the Runx1 transcription factor (TF) is elevated and that during muscle regeneration this TF regulates the balance between myoblast proliferation and differentiation (Umansky et al.). We employed Runx1-dependent gene expression, Chromatin Immunoprecipitation sequencing (ChIP-seq), Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) and histone H3K4me1/H3K27ac modification analyses to identify a subset of Runx1-regulated genes that are co-occupied by the TFs MyoD and c-Jun and are involved in muscle regeneration (Umansky et al.). The data is available at the GEO database under the superseries accession number GSE56131.

No MeSH data available.


Related in: MedlinePlus