Extended Data Fig. 5: Hnf1a upregulation perturbs HNF1A binding selectivity.
From: The HASTER lncRNA promoter is a cis-acting transcriptional stabilizer of HNF1A
a, Tissue specificity of gene expression across HNF1A-expressing tissues for genes upregulated in HasterLKO liver. To quantify tissue specificity, for each gene and tissue we calculated a Z-score that represents the deviation of expression in that tissue relative to the average from all tissues. n = 3 kidney samples, n = 5 liver and small intestine samples and n = 6 pancreatic islet samples. Box plots show medians and interquartile ranges; whiskers, 1.5 times the interquartile ranges. Two-sided Wilcoxon rank-sum P-values. b, Liver H3K4me3 and H3K27ac in HasterLKO and control liver (log2 normalized ChIP-seq read count; n = 3 mice per genotype). Red, differential H3K4me3 or H3K27ac sites (FDR ≤ 0.05); blue, kernel density of differential H3K4me3 or H3K27ac sites with FDR > 0.05. c, H3K27ac at HNF1A-bound regions in HasterLKO and controls (average of n = 3 mice per genotype). d, RNA fold change in HasterLKO vs. control liver of HNF1A-bound promoters for the different categories of HNF1A binding in HasterLKO liver. n = 5 mice per genotype for RNA and n = 3 mice per genotype for HNF1A ChIP. Box plots show medians and interquartile ranges; whiskers, 1.5 times the interquartile ranges. e, Examples of HNF1A neo-binding sites that lead to ectopic promoter and gene activation in HasterLKO liver. f, Ectopic activation of an intragenic promoter in HasterLKO liver (n = 2 mice per genotype). y axes in e and f represent MACS2 P values for ChIP-seq and RPKM for RNA-seq. g, Activated genomic regions that are bound by HNF1A and become active promoters in HasterLKO, but are inactive in control liver, overlap less frequently with annotated promoter and FANTOM5 CAGE transcriptional start sites, compared with unchanged HNF1A-bound active promoters in control liver, suggesting that some may be aberrant promoters rather that repurposed from other cell types. Two-sided Fisher’s exact test odd ratio (OR) and P-values, n = 3 mice per genotype.
