Figure 2.

SOX2 promotes differentiation toward neural lineage through occupying proneural targets in hESCs. (A) A heatmap showing epigenetic activation of a group of promoters and enhancers. Loss of H3K27me3 and gain of H3K27ac indicate a switch from poised to active promoters (left panel) and enhancers (right panel). A cluster of important neural development genes nearest to these peaks is listed. (B) A chart showing histone modification turnover of SOX2's promoter-bound genes and enhance-bound genes in hESCs to hNPCs. Repressed and unmarked histone modifications are defined as inactive ones. (C) GO analysis of genes from A whose promoter or enhancer switches from the poised state to active state. Benjamini-Hochberg method is applied to adjust the P-values in order to account for multiple testing. Enrichment levels of selected GO terms are marked by −log₂(q-value). (D) Integrative Genomics Viewer screenshots showing the density of SOX2, H3K4me3 and H3K27me3 on promoters of HES5 and DLL1 in hESCs and hNPCs. (E) ChIP-qPCR results of SOX2 enrichments at regulatory elements of Notch pathway components during neural differentiation at day 0 (hESCs), day 6 and day 25 (hNPCs). (F) Expression patterns of Notch pathway components during neural differentiation from day 0 (hESCs) to day 10. PAX6, SOX1 and OCT4 are used as controls. Scale bar represents log₂ of expression levels. (G) RT-qPCR results for Notch pathway components and proneuronal genes upon SOX2 KD in hNPCs. NT, non-targeting control; si2-1 and si2-2 are two siRNA oligos targeting SOX2.