Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity in Pluripotency and Reprogramming

http://www.cell.com/cell-stem-cell/abstract/S1934-5909(15)00159-9?rss=yes by


Figure 4

Tex10 Positively Regulates SE Activity with Sox2 in ESCs

(A) Distribution of Tex10 binding sites at promoter (−3 to +3 kb), gene body, and intergenic regions.

(B) Average ChIP-seq read density of Tex10, Sox2, Oct4, and Nanog near the Tex10 peak center.

(C) Average ChIP-seq read density of Tex10, H3K4me1, and H3K27ac near the Tex10 peak center.

(D) Tex10 binding regions are enriched for enhancers.

(E) Histograms showing percentage of genomic regions in ESC enhancer and Tex10 (only or shared with Sox2) and CTCF ChIP-seq peaks overlapping with H3K4me1 (K4me1), H3K27ac (K27ac), or both (K4me1+K27ac) peaks.

(F) Heatmaps of Tex10 binding loci are sorted by the enhancer mark H3K4me1 and the active promoter mark H3K4me3. H3K27ac is an active mark for both enhancers and promoters. ESC-specific enhancers are co-bound by Sox2, Oct4, Nanog, and Med1.

(G) Tex10 shares the majority of its targets with Med1.

(H) Distribution of Tex10, Med1, H3K4me1, and H3K27ac normalized ChIP-seq density across a subset of 8,794 ESC enhancers. For each ChIP-seq data point, we normalized the plot by dividing the ChIP-seq signals by the maximum signals individually, and we sorted them in an ascending order.

(I) The heatmap of Tex10 and Med1 intensity at 231 ESC SEs.

(J) The heatmaps of Med1 and Tex10 both show that they are enriched in SE regions.

(K) Box plot of Tex10 and Med1 ChIP-seq density (reads per million reads per base) at the SE and TE regions. Box plot whiskers extend to 1.5× the interquartile range. p values were calculated using a two-tailed t test.

(L) ChIP-seq binding profiles (reads per million per base pair) for the Tex10 and ESC TFs Oct4, Sox2, and Nanog (OSN) and Med1 at the Oct4 locus in ESCs. Gene models are depicted above the binding profiles. SE bar and scale bar are depicted above the binding profiles.

(M) Relative expression of SE-associated genes in Tex10-depleted ESCs compared with luciferase knockdown ESCs. The genes that are closest to SEs were selected. The scale represents fold changes.

See also Figure S4 .