Fig. 4: Gene expression changes driven by more accessible UL enhancers.

a Flow chart of target gene mapping of more accessible UL enhancers. We used three different methods to map target genes. Shared target genes are shared by all three UL subclasses. b Genes with UL-specific link to a more accessible enhancer tend to have higher gene expression than genes with a myometrium-specific link to a more accessible UL enhancer locus. Centre line, median; box limits, 25% and 75% quartiles; whiskers, 1.5 × interquartile range (IQR) past the quartiles. MED12 loop in UL n = 245, in myometrium n = 277, and in both n = 34 genes. HMGA2 loop in UL n = 163, in myometrium n = 77, and in both n = 17 genes. FH loop in UL n = 442, in myometrium n = 438 and in both n = 117 genes. Gene expression log2 fold change calculated previously using 38 MED12, 44 HMGA2, and 15 FH ULs, and 162 myometrium biological replicates. c Annotated target genes in at least 2 UL subclasses in each of the used methods. 64 genes were annotated as targets in at least 2/3 UL subclasses with all three methods. d Gene expression of the 64 target genes in at least 2 UL subclasses as defined through all three methods divides myometrium and UL subclasses in hierarchical clustering. e SATB2 regulatory region downstream of the gene links to TSS with HiChIP differential interactions in ULs. Figure shows GWAS SNPs associated with ULs (y-axis shows logarithmic p-value of the UL association of SNP), chromatin annotation for myometrium, MED12, HMGA2 and FH ULs and differential interactions between pooled ULs and myometrium. TssA Active TSS, TssAFlnk Flanking active TSS, TxFlnk Transcr. at gene 5’ and 3’, Tx Strong transcription, TxWk Weak transcription, EnhG Genic enhancers, Enh Enhancers, ZNF/Rpts ZNF genes + repeats, Het Heterochromatin, TssBiv Bivalent/poised TSS, BivFlnk: Flanking bivalent TSS/Enh, EnhBiv Bivalent enhancer, ReprPC Repressed Polycomb, ReprPCWk Weak repressed Polycomb, Quies Quiescent/low. Source data are provided as a Source Data file.