Ectopic expression of Ino80 complex subunit Actr5 in mouse heart
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE197087 | GEO | 2022/07/24
REPOSITORIES: GEO
Similar Datasets
Project description:Myocardin-related transcription factors (MRTFs) play a central role in the regulation of actin expression and cytoskeletal dynamics. Stimuli that promote actin polymerization allow for shuttling of MRTFs to the nucleus where they activate serum response factor (SRF), a regulator of actin and other cytoskeletal protein genes. SRF is an essential regulator of skeletal muscle differentiation and numerous components of the muscle sarcomere, but the potential involvement of MRTFs in skeletal muscle development has not been examined. We explored the role of MRTFs in muscle development in vivo by generating mutant mice harboring a skeletal muscle-specific deletion of MRTF-B and a global deletion of MRTF-A. These double knockout (dKO) mice were able to form sarcomeres during embryogenesis. However, the sarcomeres were abnormally small and disorganized, causing skeletal muscle hypoplasia and perinatal lethality. Transcriptome analysis demonstrated dramatic dysregulation of actin genes in MRTF dKO mice, highlighting the importance of MRTFs in actin cycling and myofibrillogenesis. MRTFs were also necessary for the survival of skeletal myoblasts and for the efficient formation of intact myotubes. Our findings reveal a central role for MRTFs in sarcomere formation during skeletal muscle development and point to the potential involvement of these transcriptional coactivators in skeletal myopathies. Gene expression profile was generated comparing wild type (WT) and HSA-Cre, MRTF-A/B double knockout mice, by deep seqencing, with three biological replicates, using Illumina HiSeq 2500.
2016-08-02 | E-GEOD-84063 | biostudies-arrayexpress
Project description:Myocardin-related transcription factors (MRTFs) play a central role in the regulation of actin expression and cytoskeletal dynamics. Stimuli that promote actin polymerization allow for shuttling of MRTFs to the nucleus where they activate serum response factor (SRF), a regulator of actin and other cytoskeletal protein genes. SRF is an essential regulator of skeletal muscle differentiation and numerous components of the muscle sarcomere, but the potential involvement of MRTFs in skeletal muscle development has not been examined. We explored the role of MRTFs in muscle development in vivo by generating mutant mice harboring a skeletal muscle-specific deletion of MRTF-B and a global deletion of MRTF-A. These double knockout (dKO) mice were able to form sarcomeres during embryogenesis. However, the sarcomeres were abnormally small and disorganized, causing skeletal muscle hypoplasia and perinatal lethality. Transcriptome analysis demonstrated dramatic dysregulation of actin genes in MRTF dKO mice, highlighting the importance of MRTFs in actin cycling and myofibrillogenesis. MRTFs were also necessary for the survival of skeletal myoblasts and for the efficient formation of intact myotubes. Our findings reveal a central role for MRTFs in sarcomere formation during skeletal muscle development and point to the potential involvement of these transcriptional coactivators in skeletal myopathies.
2016-08-02 | GSE84063 | GEO
Project description:Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogeninâs role in adult skeletal muscle is unclear. We sought to determine myogeninâs function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we monitored blood glucose and lactate levels and performed histochemical analysis on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle. We used microarrays to detail the global program of gene expression underlying enhanced exercise endurance associated with myog-deletion and long-term exercise training. Mouse gastrocnemius muscles were selected after 6 months of myog-deletion and exercise training for RNA extraction and hybridization on Affymetrix microarrays. We chose 3 wild type and 3 myog-deleted mice that best represented the average of each larger group that was tested during our mouse exercise studies.
2010-06-08 | E-GEOD-22046 | biostudies-arrayexpress
Project description:Smooth muscle differentiation has been proposed to sculpt airway epithelial branches in mammalian lungs. Serum response factor (SRF) acts with its cofactor myocardin to promote the expression of contractile smooth muscle markers. However, smooth muscle cells exhibit a variety of phenotypes beyond contractile that are independent of SRF-myocardin-induced transcription. To determine whether airway smooth muscle exhibits phenotypic plasticity during embryonic development, we deleted Srf from the pulmonary mesenchyme. Srf-mutant lungs branch normally, and the mesenchyme exhibits normal cytoskeletal features and patterning. scRNA-seq revealed an Srf-null smooth muscle cluster wrapping the airways of mutant lungs that lacks contractile smooth muscle markers but retains many features of control smooth muscle. Srf-null airway smooth muscle exhibits a synthetic phenotype, compared to the contractile phenotype of wildtype airway smooth muscle. Our findings reveal plasticity in mesenchymal differentiation during lung development and demonstrate that a synthetic smooth muscle layer is sufficient for airway branching morphogenesis.
2023-01-17 | GSE203171 | GEO
Project description:Purpose: Endothelial cell-specific knockout of the INO80 chromatin-remodeling complex in developing mouse embryos results in defective coronary angiogenesis. Transcriptome analysis on whole hearts was performed to understand how Ino80 regulates the genome to influence angiogenesis. Methods: mRNA was extracted from whole hearts after surgical removal from embryonic day 13.5 mice, either WT or Tie2-Ino80 KO, and prepped for Illumina sequencing using the NEBNext Ultra RNA Library Prep kit. Results: Deletion of Ino80 in the two major coronary progenetiors results in intermediate non-compaction phenotypes and an increase in E2F-mediated gene expression and cellular proliferation. Conclusions: Ino80 normally functions to suppress E2F-mediated proliferation in cardiac endothelial cells in order to promote productive angiogenesis and prevent underdevelopment of the myocardium heart muscle. Loss of this critical chromatin-remodeling function results in human disease phenotypes.
2017-11-21 | GSE98082 | GEO
Project description:Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin’s role in adult skeletal muscle is unclear. We sought to determine myogenin’s function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we monitored blood glucose and lactate levels and performed histochemical analysis on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle. We used microarrays to detail the global program of gene expression underlying enhanced exercise endurance associated with myog-deletion and long-term exercise training.
2010-05-29 | GSE22046 | GEO
Project description:Cachexia is associated with poor prognosis in patients with chronic heart failure. The underlying mechanisms of cachexia triggered heart failure progression, however, are not well understood. Here, we investigated whether the dysregulation of myokine expression from wasting skeletal muscle and impaired inter-organ crosstalk during advanced heart failure might contribute to progression of the disease. RNA sequencing analysis from wasting skeletal muscles of mice with cardiac cachexia during long-term pressure overload revealed a strongly reduced expression of Ostn. Ostn encodes for the skeletal muscle derived myokine Musclin, which had been previously implicated in the enhancement of natriuretic peptide (NP) signaling. Using newly developed skeletal muscle specific, inducible Ostn knock-out mice, we demonstrated that reduced skeletal muscle Musclin levels exaggerated cardiac dysfunction and myocardial fibrosis compared to littermate control mice after TAC. Restoration of Musclin deficiency during cardiac cachexia via AAV6-mediated skeletal muscle specific Musclin overexpression, in turn, attenuated left ventricular dysfunction and myocardial fibrosis. Mechanistically, we found that Musclin enhanced CNP/NPR2/cGMP signaling in cardiomyocytes, which led to improved contractility by inhibition of the cAMP degrading phosphodiesterase (PDE)3 and augmented cAMP/protein kinase A signaling. In addition, Musclin directly acted on cardiac fibroblasts to inhibit their activation. Together, our study indicates the therapeutic potential of targeting interorgan cross-talk during heart failure, for example by counteracting the impaired secretion of the Musclin from wasting skeletal muscle.
2021-11-02 | GSE129205 | GEO
Project description:During transcription, nucleosomes are evicted from regulatory and coding regions yet chromatin structure is stable. Restoration of chromatin structure involves concerted action of chromatin modifying activities. Our analysis demonstrates a genome wide function of the INO80 remodeling complex for stable repositioning of the nucleosome immediately proximal to the transcription initiation site. INO80 dependent remodeling of the promoter proximal nucleosomes has a global repressive role. Recruitment of INO80 to proximal nucleosomes overlaps with the elongating Polymerase II complex assembly. The amount of associated Polymerase II at start sites correlates with INO80 recruitment for inducible and constantly transcribed genes. Furthermore, at highly inducible promoters INO80 is required for repression of bidirectional transcription. Therefore, we suggest a function for INO80 after transcription initiation to achieve Polymerase II dependent reassembly of promoter proximal nucleosomes.
2016-12-24 | E-MTAB-1810 | biostudies-arrayexpress
Project description:ABSTRACT Aims Forced differentiation of non-muscle cells into heart muscle cells using cardiac transcription factors (cTFs) may constitute a novel strategy to accomplish myocardial regeneration. Methods We investigated the potential of the cTF myocardin to induce cardiomyocyte differentiation and compared the myocardin-induced gene expression program to that of fully differentiated cardiomyocytes using oligonucleotide microarray hybridizations, quantitative RT-PCR analyses and immunofluorescence microscopy. The experiments were performed in the recently described human cardiomyocytes progenitor cells (hCMPCs), which differentiate into fully functional cardiomyocytes upon stimulation with 5-azacytidine and transforming growth factor β1. Results and Conclusions Forced myocardin expression stimulated transcription of a surprisingly large repertoire of heart muscle-specific genes in hCMPCs but did not cause their differentiation into functional cardiomyocytes. Specifically, myocardin gene transfer did not stimulate the synthesis of several sarcomeric (regulatory) proteins and ion channel constituents. The heart and smooth muscle-enriched isoforms of myocardin stimulate equally well the transcription of many of their cardiomyocyte-specific and virtually all of their smooth muscle target genes. However, the heart muscle-enriched myocardin species is a much more potent transactivator of a subset of genes encoding mainly cardiomyocyte-specific myofibrillar components. This may explain the underestimation of myocardin's cardiomyogenic potential in previous studies utilizing the smooth muscle-enriched isoform of this cTF.
2008-07-15 | GSE12110 | GEO
Project description:Cardiac hypertrophy and failure are accompanied by a reprogramming of gene expression that involves transcription factors and chromatin remodeling enzymes. Little is known about the role of histone methylation and demethylation in this process. To understand the role of JMJD2A, a trimethyl demethylase for histone 3 lysine 9 and 36, in cardiac hypertrophy, we generated heart specific JMJD2A deletion (JMJD2A hKO) and overexpression (JMJD2A-Tg) mouse lines. JMJD2A hKO and JMJD2A-Tg mice are viable and have no overt baseline phenotype. However, they have altered responses to cardiac stresses. While inactivation of JMJD2A in hKO mice resulted in an attenuated hypertrophic response to transverse aortic constriction (TAC)-induced pressure overload compared to that of control littermates, JMJD2A-Tg mice have exacerbated cardiac hypertrophy after TAC. We identified four-and-a-half LIM domains 1 (FHL1) as a novel target of JMJD2A. JMJD2A binds to the FHL1 promoter in response to TAC and upregulates the expression of FHL1. Binding of JMJD2A to the FHL1 promoter is associated with downregulation of trimethylated H3K9. Upregulation of FHL1 by JMJD2A is mediated through SRF and myocardin, and requires its demethylase activity. The expression of JMJD2A is upregulated in human hypertrophic cardiomyopathy patients. Our studies reveal that JMJD2A promotes cardiac hypertrophy by synergistically upregulating SRF/myocardin-targeted genes and suggest a novel mechanism of reprogramming of gene expression involved in cardiac hypertrophy. Six to eight years old wildtype and JMJD2A heart specific transgnic mice were undergone either sham or TAC surgery. After 3 weeks, mice were sarcirificed to harvest heart. RNA was extracted from heart samples and treated with DNase, followed by biotin-labeling and microarray hybridization.
2011-06-02 | E-GEOD-27689 | biostudies-arrayexpress