Acetylation of GATA-4 Is Involved in the Differentiation of Embryonic Stem Cells into Cardiac Myocytes

Abstract

Differentiation of embryonic stem (ES) cells into cardiac myocytes requires activation of a cardiac-specific gene program. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) govern gene expression patterns by being recruited to target genes through association with specific transcription factors. One of the HATs, p300, serves as a coactivator of cardiac-specific transcription factors such as GATA-4. The HAT activity of p300 is required for acetylation and DNA binding of GATA-4 and its full transcriptional activity as well as for promotion of a transcriptionally active chromatin configuration. However,

MicroRNA-1 and MicroRNA-133 in Spontaneous Myocardial Differentiation of Mouse Embryonic Stem Cells

“…26 For infection, undifferentiated ES cells were plated on gelatinized dishes with virus-containing medium and cultured for 24 h. Infected cells were visualized as GFP-positive cells by flow cytometry (FACS Canto, BD Biosciences), as previously described. 21 …”

“…21,22 GATA4 promotes the expression of cardiac genes, such as Nkx2.5, atrial natriuretic factor (ANF), and β-myosin heavy chain (β-MHC), by forming a transcriptional complex with its coactivators, p300 and Cdk9. 23 The kinase activity of Cdk9 plays an important role in the p300-induced GATA4 acetylation, and, finally, the myocardial differentiation of mouse ES cells.…”

“…21,25 The state of undifferentiated ES cells was defined as day 0. To induce differentiation, undifferentiated ES cells were plated and 2-D cultured on gelatinized dishes without leukemia-inhibitory factor, feeder cells or the formation of EBs.…”

Embryonic Stem Cells in Toxicological Studies

“…The activities of cardiac transcription factors are regulated, in part, by histone acetyltransferases and histone deacetylases (HDACs). In the treatment of ES cells with trichostatin A (TSA), a specific HDAC inhibitor has been reported which not only induces the acetylation of both GATA4 and histones, but facilitates their differentiation into cardiomyocytes (Kawamura et al, 2005). In the very near future, it is expected that other cellular types other than hepatocytes and cardiocytes can be successfully obtained, as shown in Figure 1.…”

Cooperative interactions among intestinal GATA factors in activating the rat liver fatty acid binding protein gene

“…Interactions with cofactors or other transcription factors that bind nearby a GATA site may also mediate preferential binding or activity of individual GATA factors (4,10,12,13,30). GATA-4 is subject to phosphorylation (8,31,35,46) or acetylation (26), which can increase DNA binding. Intestinal extracts showed only GATA-4 but not GATA-6 binding to sequences containing GATA binding sites despite the presence of both factors in this tissue, suggesting regulation of binding (4,14).…”