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.
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.
Stem Cell Reports. 2018 Jan 9;10(1):287-299. doi: 10.1016/j.stemcr.2017.11.009. Epub 2017 Dec 14.
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.
在胚胎发育过程中，转录因子和共调节因子（包括染色质修饰因子）精确地调控基因表达。然而，特定的染色质修饰酶如何影响特定的发育过程还没有明确的定义。在这里，我们报告了组蛋白乙酰转移酶 GCN5 对于胚胎发育是必需的，它对于早期胚胎体（EB）中多个编码成纤维细胞生长因子（FGF）信号通路组成部分的基因的正常表达是必需的。Gcn5 EB 显示 ERK 和 p38 的激活不足、细胞骨架成分的定位错误以及向中胚层谱系分化的能力受损。基因组分析确定了七个基因是 GCN5 在早期分化过程中的潜在直接靶标，其中四个是 cMYC 的靶标。这些发现建立了 GCN5 与 FGF 信号通路之间的联系，并强调了在早期分化过程中 GCN5-MYC 特定伙伴关系在基因调控中的作用。
