Extended Data Fig. 4: Sox2 overexpression creates new super-enhancers (SE) and activates cancer promoting genes.
From: Reprogramming of the esophageal squamous carcinoma epigenome by SOX2 promotes ADAR1 dependence
a, The percentage of super-enhancers harboring gained Sox2 binding sites (left) or gained chromatin open sites (right). The super-enhancers are categorized as ‘Gained’, ‘Shared’ and ‘Lost’ based on the comparison between SCPP and Normal organoids. Gained Sox2 sites or chromatin open sites refer to the ones gained in SCPP organoids compared to Normal organoids. b, Venn diagram showing overlap of gained SEs with Sox2 binding sites gained in SCPP (vs. Normal) and gained SEs with open chromatin sites, defined by ATAC-seq in SCPP (vs. Normal). c, Venn diagram showing overlap of gained SEs in SCPP (vs Normal) and the Cancer Gene Census. d, mRNA expression levels of Il6ra and Stat3 mRNA in 4 groups organoids by quantitative RT-PCR. Data are shown as Mean ± SD. NS: not significant and p-value calculated by two-sided unpaired t-tests. Three independent biological replicates were performed for each organoid. e, Immunoblot of p-Stat3 and total Stat3 in different organoids (representative image from 3 independent experiments) (up), and the quantification of the p-Stat3 expression in different organoids (down). f, Venn Diagram shows the overlap of super-enhancers that are gained in SCPP (vs. Normal) and shared super-enhancers across three ESCC cell lines (TT, TE10 and KYSE70). P < 0.0001 calculated by two-sided fisher exact test (ESCC super-enhancer unrelated genes as control). g, Representative SOX2 and H3K27ac ChIP-seq tracks showing super-enhancers at STAT3 and IL6R locus in ESCC cell lines TE10 and TT. h, Immunoblot of p-STAT3 and total STAT3 in ESCC cell line TE10 and TT after shRNA-mediated SOX2 silencing (representative image from 2 independent experiments).
