Gcn5 regulates FGF signaling outputs through c-Myc during early differentiation of embryoid bodies
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE104454 | GEO | 2017/12/14
SECONDARY ACCESSION(S): PRJNA412653
REPOSITORIES: GEO
Similar Datasets
Project description:Precise control of gene expression during development is orchestrated by transcription factors and co-regulators including chromatin modifiers. How particular chromatin modifying enzymes affect specific developmental processes is not well defined. Here we report that Gcn5, a HAT essential for embryonic development, is largely required for c-MYC target gene transcription downstream of FGF signaling in early embryoid bodies (EBs). Gcn5 null EBs display deficient activation of ERK and p38, disorganized cytoskeletal networks, and compromised capacity to differentiate toward mesodermal and endodermal lineages. These findings establish a regulatory role for Gcn5 in execution of a critical signaling pathway during early development.
2017-12-14 | GSE104453 | GEO
Project description:Precise control of gene expression during development is orchestrated by transcription factors and co-regulators including chromatin modifiers. How particular chromatin modifying enzymes affect specific developmental processes is not well defined. Here we report that Gcn5, a HAT essential for embryonic development, is largely required for c-MYC target gene transcription downstream of FGF signaling in early embryoid bodies (EBs). Gcn5 null EBs display deficient activation of ERK and p38, disorganized cytoskeletal networks, and compromised capacity to differentiate toward mesodermal and endodermal lineages. These findings establish a regulatory role for Gcn5 in execution of a critical signaling pathway during early development.
2017-12-14 | GSE104452 | GEO
Project description:Precise control of gene expression during development is orchestrated by transcription factors and co-regulators including chromatin modifiers. How particular chromatin-modifying enzymes affect specific developmental processes is not well defined. Here, we report that GCN5, a histone acetyltransferase essential for embryonic development, is required for proper expression of multiple genes encoding components of the fibroblast growth factor (FGF) signaling pathway in early embryoid bodies (EBs). Gcn5-/- EBs display deficient activation of ERK and p38, mislocalization of cytoskeletal components, and compromised capacity to differentiate toward mesodermal lineage. Genomic analyses identified seven genes as putative direct targets of GCN5 during early differentiation, four of which are cMYC targets. These findings established a link between GCN5 and the FGF signaling pathway and highlighted specific GCN5-MYC partnerships in gene regulation during early differentiation.
| S-EPMC5768892 | biostudies-literature
Project description:Gcn5 regulates FGF signaling outputs through c-Myc during early differentiation of embryoid bodies
| PRJNA412653 | ENA
Project description:Gcn5 regulates FGF signaling outputs through c-Myc during early differentiation of embryoid bodies [RNA-Seq]
| PRJNA412660 | ENA
Project description:Gcn5 regulates FGF signaling outputs through c-Myc during early differentiation of embryoid bodies [ChIP-Seq]
| PRJNA412661 | ENA
Project description:Embryonic stem cells (ESCs) are an established model for investigating developmental processes, disease conditions, tissue regeneration and therapeutic targets. Previous studies have shown that tripartite motif-containing 33 protein (Trim33) functions as a chromatin reader during Nodal-induced mesoderm induction. Here we report that despite reduced proliferation, mouse ESCs deficient in Trim33 remained pluripotent when cultured under non-differentiating conditions. However, when induced to differentiate to embryoid bodies (EBs), the mutant cultures showed increased cell shedding and apoptosis at day 3 of differentiation. Gene set enrichment analysis (GSEA) indicated that several molecular functions associated with cell survival, transcriptional/translational activity and growth factor signaling were affected already by the second day of differentiation in Trim33-deficient EBs. Consistent with increased apoptosis, expression of Rac1, a critical factor for EB cell survival, was reduced in Trim33 mutant EBs. In addition, a set of genes involved in regulation of pluripotency was upregulated in mutant EBs. Our results suggest that Trim33 regulates early maturation of mouse embryoid bodies in vitro.
| S-EPMC5650645 | biostudies-literature
Project description:Extensive research in the field of stem cells and developmental biology has revealed evidence of the role of hypoxia as an important factor regulating self-renewal and differentiation. However, comprehensive information about the exact hypoxia-mediated regulatory mechanism of stem cell fate during early embryonic development is still missing. Using a model of embryoid bodies (EBs) derived from murine embryonic stem cells (ESC), we here tried to encrypt the role of hypoxia-inducible factor 1? (HIF1?) in neural fate during spontaneous differentiation. EBs derived from ESC with the ablated gene for HIF1? had abnormally increased neuronal characteristics during differentiation. An increased neural phenotype in Hif1?-/- EBs was accompanied by the disruption of ?-catenin signaling together with the increased cytoplasmic degradation of ?-catenin. The knock-in of Hif1?, as well as ?-catenin ectopic overexpression in Hif1?-/- EBs, induced a reduction in neural markers to the levels observed in wild-type EBs. Interestingly, direct interaction between HIF1? and ?-catenin was demonstrated by immunoprecipitation analysis of the nuclear fraction of wild-type EBs. Together, these results emphasize the regulatory role of HIF1? in ?-catenin stabilization during spontaneous differentiation, which seems to be a crucial mechanism for the natural inhibition of premature neural differentiation.
| S-EPMC5750467 | biostudies-literature
Project description:Independent mouse knockouts of Etv2 and Flk1 are embryonic lethal and lack hematopoietic and endothelial lineages. We previously reported that Flk1 activates Etv2 in the initiation of hematopoiesis and vasculogenesis. However, Flk1 and its ligand VEGF are expressed throughout development, from E7.0 to adulthood, whereas Etv2 is expressed only transiently during embryogenesis. These observations suggest a complex regulatory interaction between Flk1 and Etv2. To further examine the Flk1 and Etv2 regulatory interaction, we transduced Etv2 and Flk1 mutant ES cells with viral integrants that inducibly overexpress Flk1 or Etv2. We demonstrated that forced expression of Etv2 rescued the hematopoietic and endothelial potential of differentiating Flk1 and Etv2 mutant cells. We further discovered that forced expression of Flk1 can rescue that of the Flk1, but not Etv2 mutant cells. Therefore, we conclude that the requirement for Flk1 can be bypassed by expressing Etv2, supporting the notion that disruption of Etv2 expression is responsible for the early phenotypes of the Etv2 and Flk1 mutant embryos.
| S-EPMC3987665 | biostudies-literature
Project description:The neurocranium generates most of the craniofacial skeleton and consists of prechordal and postchordal regions. Although development of the prechordal is well studied, little is known of the postchordal region. Here we characterize a signaling hierarchy necessary for postchordal neurocranial development involving Fibroblast growth factor (Fgf) signaling for early specification of mesodermally-derived progenitor cells. The expression of hyaluron synthetase 2 (has2) in the cephalic mesoderm requires Fgf signaling and Has2 function, in turn, is required for postchordal neurocranial development. While Hedgehog (Hh)-deficient embryos also lack a postchordal neurocranium, this appears primarily due to a later defect in chondrocyte differentiation. Inhibitor studies demonstrate that postchordal neurocranial development requires early Fgf and later Hh signaling. Collectively, our results provide a mechanistic understanding of early postchordal neurocranial development and demonstrate a hierarchy of signaling between Fgf and Hh in the development of this structure.
| S-EPMC4967541 | biostudies-literature