Fig. 3: Enhancer malfunction leads to gene expression changes in leiomyomas.

a Venn diagram of promoter contacts overlapping differentially acetylated H3K27 regions in myometrium and leiomyoma tissue. HindIII digest fragments of the human genome are used to define unique, non-overlapping regions in the genome, to which H3K27Ac peaks and promoter contacts are then assigned. See CHi-C data processing and analysis in Methods. b Heat scatter plot of fold change in gene expression against fold change in H3K27Ac signal at enhancers associated with differentially expressed genes (n = 2715 enhancer regions). c Heat map of altered promoter contacts associated with differentially expressed genes (n = 2040 contacts). d Scatter plot of confidence scores for enriched gene ontologies associated with altered promoter contacts linked to differentially expressed genes, with ontologies clustered by functional similarity in the semantic space. e Heat maps of altered enhancer-promoter contacts that overlap with increasing H3K27Ac (top panel, n = 903 contacts) and decreasing H3K27Ac (bottom panel, n = 396 contacts) at enhancer regions in myometrium and leiomyoma tissues. f, g Genomic loci for FN1 (f) and COL12A1 (g) genes, which both have unchanged H3K27Ac signal at promoters. Altered confidence scores (CHiCAGO q-scores) are shown for myometrium and leiomyoma. In addition, H3K27Ac ChIP-seq and RNA-seq genomic tracks are shown, with H3K27Ac and RNAPII ChIP-seq signal in regions containing altered contacts highlighted (bottom zoomed in inset).