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Gcn5 regulates FGF signaling outputs through c-Myc during early differentiation of embryoid bodies [ChIP-Seq]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE104452 | GEO | 2017/12/14

SECONDARY ACCESSION(S): PRJNA412661

REPOSITORIES: GEO

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Gcn5 regulates FGF signaling outputs through c-Myc during early differentiation of embryoid bodies [RNA-Seq]

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.

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Gcn5 regulates FGF signaling outputs through c-Myc during early differentiation of embryoid bodies

Project description:Gcn5 regulates FGF signaling outputs through c-Myc during early differentiation of embryoid bodies

| PRJNA412653 | ENA

Gcn5 regulates FGF signaling outputs through c-Myc during early differentiation of embryoid bodies

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-12-14 | GSE104454 | GEO

Differential requirements for Gcn5 and NuA4 HAT activities in the starvation-induced versus basal transcriptomes

Project description:The histone acetyltransferase (HAT) subunit of coactivator complex SAGA, Gcn5, is required for efficient eviction of promoter nucleosomes at certain highly expressed yeast genes, including those activated by transcription factor Gcn4 in amino acid-deprived cells; however, the importance of other HAT complexes in this process was poorly understood. Analyzing mutations that disrupt the integrity or activity of HAT complexes NuA4 or NuA3, or the HAT Rtt109, revealed that only NuA4 acts on par with Gcn5, and functions additively, in evicting and repositioning promoter nucleosomes and stimulating transcription of starvation-induced genes. NuA4 is generally more important than Gcn5, however, in promoter nucleosome eviction, TBP recruitment, and transcription at most other genes expressed constitutively. NuA4 also predominates over Gcn5 in stimulating TBP recruitment and transcription of genes categorized as principally dependent on the cofactor TFIID versus SAGA, except for the highly expressed subset encoding ribosomal proteins (RPs), where Gcn5 contributes strongly to PIC assembly and transcription. Both SAGA and NuA4 are recruited to promoter regions of SM-induced genes in a manner that appears to be feedback controlled by their HAT activities. Our findings reveal an intricate interplay between these two HATs in nucleosome eviction, PIC assembly, and transcription that differs between the starvation-induced and basal transcriptomes.

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PCAF/GCN5-regulated genes in MEFs

Project description:Histone acetyltransferases (HATs) GCN5/PCAF and CBP/p300 are transcription coactivators. However, how these HATs regulate ligand-induced nuclear receptor target gene expression remains unclear. Here we show in mouse embryonic fibroblasts (MEFs), deletion of GCN5/PCAF specifically eliminates acetylation on H3K9 (H3K9Ac) while deletion of CBP/p300 selectively reduces acetylation on H3K18 and H3K27 (H3K18/27Ac). Treating MEFs with a specific ligand for nuclear receptor PPARdelta induces sequential increases of H3K18/27Ac and H3K9Ac on the promoter of PPARdelta target gene Angptl4, which correlates with a robust ligand-induced Angptl4 expression. Inhibiting transcription elongation blocks ligand-induced H3K9Ac but not H3K18/27Ac on Angptl4 promoter. Finally, we show CBP/p300 and their HAT activities are required, while GCN5/PCAF and H3K9Ac are dispensable, for ligand-induced PPARdelta target gene expression in MEFs. These results highlight the substrate and site specificities of HATs in cells, and suggest that GCN5/PCAF- and CBP/p300-mediated histone acetylations play distinct roles in regulating ligand-induced nuclear receptor target gene expression. PCAF and GCN5 have some redundant function. To identify PCAF/GCN5-regulated genes, immortalized MEFs with PCAF knockout and GCN5 conditional knockout were infected with retroviruses expressing either Cre recombinase or vector alone. We prepared duplicated RNAs from either vector or Cre infected cells (PCAF-/-;GCN5+/- or PCAF-/-;GCN5+/-) and RNAs from either Vector or Cre infected the other independently immortalized cells for 6 affymetrix microarray.

2013-12-31 | E-GEOD-20008 | biostudies-arrayexpress

Gcn5 regulates FGF signaling outputs through c-Myc during early differentiation of embryoid bodies [RNA-Seq]

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

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Gcn5 regulates FGF signaling outputs through c-Myc during early differentiation of embryoid bodies [ChIP-Seq]

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

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GCN5 Regulates FGF Signaling and Activates Selective MYC Target Genes during Early Embryoid Body Differentiation.

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.

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