Modulating MyoD1 dosage activates alternate cell fate beyond myogenic differentiation [ATAC-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE309864 | GEO | 2026/06/03
REPOSITORIES: GEO
Similar Datasets
Project description:Transcription factor (TF) expression and dosage regulate developmental cell fate decisions. Increased TF dosage has been predicted to enhance expression of high-affinity target genes but also increase the binding of lower-affinity loci. The relative importance of high- versus lower-affinity TF binding in guiding cell fate decisions remains unclear. To test the roles of TF dosage, we examined the effects of increasing the dosage of MyoD1, the “master regulator of myogenesis”, on skeletal muscle differentiation. Unexpectedly, increased MyoD1 dosage inhibited canonical myogenesis and redirected myoblast differentiation towards forming spontaneously contracting myotubes. This novel phenotype was driven by the MyoD1-dose-dependent upregulation of non-myogenic genes, including cell adhesion genes whose ectopic expression also inhibited classical myogenic differentiation and enabled myotube contraction. Live-cell single-molecule imaging showed that elevated MyoD1 dosage increased total chromatin binding and CUT&RUN profiling demonstrated that this increase occurred via preferential binding to lower-affinity loci. Integration of CUT&RUN, ATAC-seq and RNA-seq experiments revealed that increased MyoD1 binding correlated to the upregulation of otherwise unexpressed or lowly expressed genes. These findings suggest that increased MyoD1 dosage induced a selective gene regulatory expansion from high- to lower-affinity cis-regulatory elements, leading to activation of a broader ensemble of target genes, revealing a TF dose-dependent mechanism that can trigger distinct developmental programs.
2026-06-03 | GSE309919 | GEO
Project description:Transcription factor (TF) expression and dosage regulate developmental cell fate decisions. Increased TF dosage has been predicted to enhance expression of high-affinity target genes but also increase the binding of lower-affinity loci. The relative importance of high- versus lower-affinity TF binding in guiding cell fate decisions remains unclear. To test the roles of TF dosage, we examined the effects of increasing the dosage of MyoD1, the ?master regulator of myogenesis?, on skeletal muscle differentiation. Unexpectedly, increased MyoD1 dosage inhibited canonical myogenesis and redirected myoblast differentiation towards forming spontaneously contracting myotubes. This novel phenotype was driven by the MyoD1-dose-dependent upregulation of non-myogenic genes, including cell adhesion genes whose ectopic expression also inhibited classical myogenic differentiation and enabled myotube contraction. Live-cell single-molecule imaging showed that elevated MyoD1 dosage increased total chromatin binding and CUT&RUN profiling demonstrated that this increase occurred via preferential binding to lower-affinity loci. Integration of CUT&RUN, ATAC-seq and RNA-seq experiments revealed that increased MyoD1 binding correlated to the upregulation of otherwise unexpressed or lowly expressed genes. These findings suggest that increased MyoD1 dosage induced a selective gene regulatory expansion from high- to lower-affinity cis-regulatory elements, leading to activation of a broader ensemble of target genes, revealing a TF dose-dependent mechanism that can trigger distinct developmental programs. This submission contains additional RNA-seq samples generated that should be added to existing GEO Series GSE309864.
2026-06-03 | GSE309939 | GEO
Project description:C2C12 is a myoblast cell line usually used for study of muscle differentiation. Myod1 is a pro-differentiation factor for myogenesis. We found that CRISPR/Cas9-mediated Myod1 gene knockout in C2C12 cells led to the loss of myoblast identity and gain of neural properties.
2021-01-27 | GSE137507 | GEO
Project description:In this study, Affymetrix MG_U74Av2 and MG_U74Cv2 GeneChips were used to analyze gene expression over a 12 day time course in C2C12 myoblasts induced to differentiate in vitro. Triplicate cultures were studied during cell proliferation (days -2 and -1), at cell cycle withdrawal (day 0) and during myogenic fusion and maturation of multinucleated myotubes (days 2, 4, 6, 8, 10). The manuscript associated to this work is Tomczak et al., FASEB J., 2003 Dec 19. Additionally, the supplementary data can be found on our homepage at http://www.chb-genomics.org/beggslab/ Keywords = C2C12 myoblasts Keywords = myogenesis Keywords: time-course
2004-01-24 | GSE990 | GEO
Project description:In this study, Affymetrix MG_U74Av2 and MG_U74Cv2 GeneChips were used to analyze gene expression over a 12 day time course in C2C12 myoblasts induced to differentiate in vitro. Triplicate cultures were studied during cell proliferation (days -2 and -1), at cell cycle withdrawal (day 0) and during myogenic fusion and maturation of multinucleated myotubes (days 2, 4, 6, 8, 10). The manuscript associated to this work is Tomczak et al., FASEB J., 2003 Dec 19. Additionally, the supplementary data can be found on our homepage at http://www.chb-genomics.org/beggslab/ Keywords = C2C12 myoblasts Keywords = myogenesis Keywords: time-course
2004-01-24 | GSE989 | GEO
Project description:C2C12 mouse myoblasts expressing RAS mutants identified in human tumors fail to differentiate in low serum media.
2018-04-01 | GSE85168 | GEO
Project description:In this study we performed transcriptome analysis (bulk RNAseq) of WT-C2C12 immortalized mouse myoblasts and FlncKO-C2C12 cells during myogenic differentiation (day 0, 1, 2, 4 and 6).
2025-12-16 | GSE312993 | GEO
Project description:Skeletal muscle differentiation is a highly coordinated multistep process in which proliferating mononucleated myoblasts first withdraw from the cell cycle, then differentiate into postmitotic mononucleated myocytes, and subsequently fuse into multinucleated myotubes which finally bundle to form mature muscle fibers. All these processes are controlled by the sequential activation of myogenic regulatory factors, and especially MYOD1 is activated in the early phase to promote the transcription of muscle-specific genes coding for muscle proteins such as alpha-actin, myosin heavy chain and muscle creatine kinase. We used microarrays to detail the global gene expression changes associated with MYOD1 L122R mutation and identified MYOD1 L122R blocked myogenic differentiation and had a MYC-like transcriptional potential. C2C12 mouse myoblast cells were introduced wild type MYOD1, MYOD1 L122R, MYC, and GFP by retroviral infection. For retrovirus production, the pcx4 and pBabe vectors system were used. Retroviruses were obtained by using 293T cells as packaging cells, and were infected into C2C12 cell line and selected with 500 μg/ml Zeocin (Invitrogen, Carlsbad, CA, USA). After selection, RNAs were extracted and processed at MSKCC according to procedures recommended by Affymetrix (Santa Clara, CA, USA).
2014-05-01 | E-GEOD-56079 | biostudies-arrayexpress
Project description:We generated the human ES lines, in which the genome-wide reduction of H3K27me3 can be induced by the ectopic expression of catalytic domain of histone demethylase JMJD3 with doxycycline treatment (JMJD3c-hESCs). The overexpression of JMJD3c enhances MYOD1-mediated myogenic differentiation of hESCs. We compared the gene expression patterns of the generated myogenic cells with those of human skeletal myotubes.
2016-10-18 | GSE80106 | GEO
Project description:Spatial organization of the mammalian genome influences gene expression and cell identity. While association of genes with the nuclear periphery is commonly linked to transcriptional repression, also active, expressed genes can localize at the nuclear periphery. The transcriptionally active MyoD1 gene, a master regulator of myogenesis, exhibits peripheral localization in proliferating myoblasts, yet the underlying mechanisms remain elusive. Using a newly generated reporter cell line, we demonstrate here that peripheral association of the MyoD1 locus is independent of mechanisms involved in heterochromatin anchoring. We identify a set of nuclear envelope transmembrane proteins, particularly WFS1, that actively tether MyoD1 to the nuclear periphery. WFS1 primarily associates with active distal enhancer elements upstream of MyoD1, and with a subset of enhancers enriched in active histone marks genome-wide, which are linked to expressed myogenic genes. Overall, our data identify a novel mechanism involved in tethering active genes to the nuclear periphery. This research was funded in whole or in part by the Austrian Science Fund (FWF) [P29713-B28, P32512-B and P36503-B] to Roland Foisner and a doctorate program funded by the Austrian Science Fund (FWF) [W1261-B28].
2025-01-20 | GSE253460 | GEO