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

Stem Cell Reports. 2018 Jan 9;10(1):287-299. doi: 10.1016/j.stemcr.2017.11.009. Epub 2017 Dec 14.

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 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.

Keywords: FGF signaling; GCN5; MYC; acetylation; chromatin; embryoid body; histone H3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Embryoid Bodies / cytology
  • Embryoid Bodies / metabolism*
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism*
  • MAP Kinase Signaling System*
  • Mice
  • Mice, Knockout
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • p300-CBP Transcription Factors / genetics
  • p300-CBP Transcription Factors / metabolism*
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Myc protein, mouse
  • Proto-Oncogene Proteins c-myc
  • Fibroblast Growth Factors
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • p38 Mitogen-Activated Protein Kinases