Extended Data Fig. 5: HHEX and FOXA2 ChIP-MS and ChIP-seq analysis. | Nature Cell Biology

Extended Data Fig. 5: HHEX and FOXA2 ChIP-MS and ChIP-seq analysis.

From: CRISPR screening uncovers a central requirement for HHEX in pancreatic lineage commitment and plasticity restriction

Extended Data Fig. 5

a, Venn diagram showing significantly enriched proteins at the GT and PP1 stages for HHEX ChIP-MS. b, GREAT Gene Ontology showing the top 7 biological processes associated with the FOXA2-down regions with the P values indicated. The terms were selected based on the rank from the binomial test and cut-offs of region fold enrichment >1.5 and observed regions >80. c, IGV tracks (average of two independent experiments) showing chromatin accessibility and TFs binding activities at the PDX1 (left) and SOX9 (right) loci in WT and KO cells. Tracks are generated from two independent experiments. Scale bars are indicated. Regions that showed significantly decreased FOXA2 binding upon HHEX deletion are indicated by dashed boxes. d, MA plot showing differential FOXA2 binding (blue) at the PP2 stage following HHEX deletion. The number of significantly increased and decreased FOXA2 binding sites is indicated. e, TF motifs enriched in regions with differential FOXA2 binding upon HHEX deletion. Regions with significantly increased/decreased FOXA2 binding were compared with the FOXA2 ChIP-seq atlas to examine TF motif enrichments using one-sided KS test. The KS test effect size is shown on the y axis, and the proportion of peaks associated with the TF motif is plotted on the x axis. The size of each circle represents the odds ratio, which was defined as the frequency of a given TF motif in regions with increased or decreased FOXA2 binding divided by its frequency in the FOXA2 ChIP-seq atlas. TF motifs with a KS test effect size ≥ 0.1 (indicated by the dashed lines) and odds ratio ≥ 1.2 are shown. f, Volcano plot showing enriched proteins (purple) for FOXA2 ChIP-MS at the PP2 stage in WT versus KO cells. Dotted lines indicate the fold change and significance cut-offs (|log2(FC)| > 1, –log2(P) > 4.32). CDX2 (log2 (FC) = –2.01, P = 0.067) is also indicated. Data shown in a-e are from two independent experiments, and data shown in f represent three independent experiments.

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