ChIP-seq profiling of myogenin and p300 occupancy in the context of rexinoid signaling during early myogenic differentiation
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PROVIDER: PRJNA587703 | ENA |
REPOSITORIES: ENA
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Project description:Deciphering the molecular mechanisms underpinning myoblast differentiation is a critical step in developing the best strategy to promote muscle regeneration in patients suffering from muscle-related diseases. We have previously established that a rexinoid x receptor (RXR)-selective agonist enhances the differentiation and fusion of myoblasts through a direct regulation of MyoD expression, coupled with an augmentation of myogenin protein. Here, we found that RXR signaling modifies the chromatin state distribution of myogenin, promoting the binding preference of myogenin for poised enhancers and a distinct motif. We also found an association of myogenin with rexinoid-responsive gene expression and identified an epigenetic signature related to histone acetyltransferase p300. Moreover, RXR signaling instigates residue-specific histone acetylation at enhancers co-occupied by p300 and myogenin. Thus, genomic distribution of transcriptional regulators is an important designate for identifying novel targets as well as developing therapeutics that modulate epigenetic landscape in a selective manner to promote muscle regeneration.
2020-06-24 | GSE139942 | GEO
Project description:While skeletal myogenesis is tightly coordinated by myogenic regulatory factors including MyoD and myogenin, chromatin modifications have emerged as vital mechanisms of myogenic regulation. We have previously established that bexarotene, a clinically approved agonist of retinoid X receptor, promotes the specification and differentiation of skeletal muscle lineage. Here, we examine a genome-wide impact of rexinoids on myogenic differentiation through integral RNA-seq and ChIP-seq analyses. We found that bexarotene promotes myoblast differentiation through the coordination of exit from the cell cycle and the activation of muscle-related genes. We uncovered a new mechanism of rexinoid action which is mediated by the nuclear receptor and largely reconciled through a direct regulation of MyoD gene expression. In addition, we determined a rexinoid-responsive residue-specific histone acetylation at a distinct chromatin state associated to MyoD and myogenin. Thus, we provide novel molecular insights into the interplay between retinoid X receptor signaling and chromatin states pertinent to myogenic programs in early myoblast differentiation.
2017-09-13 | GSE94558 | GEO
Project description:Molecular regulation of stem cell differentiation is exerted through both genetic and epigenetic determinants over distal regulatory or enhancer regions. Understanding the mechanistic action of active or poised enhancers is thus imperative for control of stem cell differentiation. Based on a genome-wide co-occurrence of different epigenetic marks in committed proliferating myoblasts, we have previously generated a 14-state chromatin state model to profile residue-specific histone acetylation in early myoblast differentiation. Here, we use genome-wide chromatin state association to delineate the functional mode of transcription regulators in early myogenic differentiation. We define a role of transcriptional coactivator p300, when recruited by master muscle regulator MyoD, in the establishment and regulation of myogenic loci at the onset of terminal differentiation. In addition, we reveal an enrichment of residue- and loci-specific histone acetylation at p300 associated active or poised enhancers, particularly when enlisted by MyoD. We provide novel molecular insights into the regulation of myogenic enhancers by p300 in concert with MyoD. Our studies present a valuable aptitude for driving stage specific chromatin state or enhancers pharmacologically to treat muscle related diseases and for the identification of additional myogenic targets and molecular interactions for therapeutic development.
2018-07-30 | GSE109636 | GEO
Project description:While skeletal myogenesis is tightly coordinated by myogenic regulatory factors including MyoD and myogenin, chromatin modifications have emerged as vital mechanisms of myogenic regulation. We have previously established that bexarotene, a clinically approved agonist of retinoid X receptor, promotes the specification and differentiation of skeletal muscle lineage. Here, we examine a genome-wide impact of rexinoids on myogenic differentiation through integral RNA-seq and ChIP-seq analyses. We found that bexarotene promotes myoblast differentiation through the coordination of exit from the cell cycle and the activation of muscle-related genes. We uncovered a new mechanism of rexinoid action which is mediated by the nuclear receptor and largely reconciled through a direct regulation of MyoD gene expression. In addition, we determined a rexinoid-responsive residue-specific histone acetylation at a distinct chromatin state associated to MyoD and myogenin. Thus, we provide novel molecular insights into the interplay between retinoid X receptor signaling and chromatin states pertinent to myogenic programs in early myoblast differentiation.
2017-09-13 | GSE94560 | GEO
Project description:ChIP-seq profiling of transcriptional co-activator p300 during early myogenic differentiation
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Project description:We characterized the genome wide occupancy of Med12 and p300 in mouse HSPCs. We also characterize p300 occupancy upon shRNA against control or Med12. ChIP-seq analysis of Med12 and/or p300 in untreated HSPCs
2016-08-25 | E-GEOD-76053 | biostudies-arrayexpress
Project description:We characterized the genome wide occupancy of Med12 and p300 in mouse HSPCs. We also characterize p300 occupancy upon shRNA against control or Med12.
2016-08-25 | GSE76053 | GEO
Project description:Different approaches of skeletal muscle cell regeneration originated from progenitor cells are extensively studied under the strategies of muscle tissue pathologies treatment. Recently it was discovered that anatomically localized alveolar mucosa multipotent mesenchymal stromal cells (AMC) are characterized by myogenic potential and high feasibility for muscle tissue recovery and regeneration. Although the resulting multinuclear myotubes are featured by expressing skeletal muscle specific markers (skeletal myosin, actin, myogenin and MyoD1) the exact molecular mechanism controlling differentiation of AMC in myogenic direction is still unclear and poorly scrutinized. In this research we used combination of large-scale transcriptome analysis and bioinformatics approach to appreciate molecular pathways and crucial nodes responsible for myogenic differentiation.
2019-07-13 | GSE134207 | GEO
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.
2024-01-10 | GSE194030 | GEO
Project description:Zinc finger E-box-binding homeobox 2 (ZEB2, also known as SMAD interacting protein 1 or Zfhx1b) protein is a transcription factor involved in the transforming growth factor β (TGFβ) and bone morphogenetic proteins (BMPs) signaling pathways. ZEB2 is a two-handed zinc-finger closely related to ZEB1 (ZFHX1a/δEF1) and it is present in many tissues including cardiac and skeletal muscles. Skeletal muscle development and adult myogenesis are regulated by helix-loop-helix proteins, including MyoD, Myf5, myogenin and MRF-4. It has been shown that ZEB1 (ZFHX1a/δEF1) competes with the myogenic regulatory factors for their consensus sequences on some target genes during muscle differentiation, however the role of ZEB2 in myogenesis is still unknown. In the present study, we evaluated the myogenic potential of Zeb2-null and R26_Zeb2 mouse embryonic stem cells by single-cell RNA-sequencing and tested muscle engraftment capability of the respective myogenic progenitors. Our results support the implication of Zeb2 in promoting myogenesis in pluripotent stem cells and myogenic progenitors by modulating specific genes encoding components of the TGFβ/BMP signaling system.
2020-03-31 | GSE147744 | GEO