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

Stem Cell Reports

Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA; Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA; Program in Epigenetics and Molecular Carcinogenesis, The Graduate School of Biomedical Sciences (GSBS) of the University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Program in Genes and Development, The Graduate School of Biomedical Sciences (GSBS) of the University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address:

Published: January 2018

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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768892PMC
http://dx.doi.org/10.1016/j.stemcr.2017.11.009DOI Listing

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