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 [ChIP-Seq]
| PRJNA412661 | ENA
Project description:Gcn5 regulates FGF signaling outputs through c-Myc during early differentiation of embryoid bodies [RNA-Seq]
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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.
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