Figure 1. Key regulators of cardiac differentiation share a temporal chromatin signature.

At five different time points of directed differentiation of human embryonic stem cells into cardiomyocytes (T0, 2, 5, 9 and 14), the levels of histone modifications H3K4me3 (activating), H3K27me3 (repressing) and H3K36me3 (transcribed) are shown within a ~50 kb region around (A) NKX2-5, a well-known regulator of cardiac differentiation (scales used: 1 to 250/150/50 tags per 150 bp, for H3K4me3/H3K27me3/H3K36me3) and (B) MYH6, a well-known structural component of cardiac cells (scales used: 1 to 500/100/50 tags per 150 bp, for H3K4me3/H3K27me3/H3K36me3). The relative levels of histone modifications (red, green and blue) and RNA expression (purple) are shown for (C) selected regulators of cardiac differentiation and (D) cardiac structural factors at all five time points. The averaged levels of epigenetic marks within ±20 kb of the TSS of (E) known regulators of cardiac differentiation and (F) known cardiac structural factors are plotted across all five time points (0, 2, 5, 9 14 = green, yellow, red, blue, purple). For key regulators of cardiac differentiation, levels of H3K4me3 and H3K36me3 increase during differentiation while H3K27me3 begins high and decreases, while H3K27 remains consistently low for cardiac structural factors. Note GATA4 is shown twice in panel (c) due to activation of two different promoters in our system. See Figure S3 for patterns found for other gene groups.