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Fig. 8 | BMC Biology

Fig. 8

From: Activation function 1 of progesterone receptor is required for progesterone antagonism of oestrogen action in the uterus

Fig. 8

Evidence for the genomic mechanism of antagonism to ESR1 by PGR. A AF1 mutations caused upregulation of Esr1, Greb1, and some other genes (Zbtb1, Rmnd1, Armt1, Cdc170, and Syne1) in the ESR1-TAD. The results were obtained by qPCR of GD3 uterine samples and expressed as the relative change to housekeeping gene 36b4 (mean ± SEM, n = 6). B AF1 mutations alter the chromatin interactions in the Esr1 (left side) and Greb1 (right side) loci in the uterus. Top panel: composite illustration of intermingled ESR1 and PGR binding sites in the Esr1 and Greb1 gene loci in the uterus in the absence (Ctrl) or presence of oestrogen (ES) or progesterone (Pg). The enrichment of histone marks, H3K27ac, and H3K4me1 around the cluster of PGR and ESR1 binding sites indicates active enhancers. The CTCF binding data were from mouse liver. The chromatin binding data were obtained from the ChIP-Atlas (peak call q < 1E−10). The cluster of binding sites of ESR1 and PGR between the Ccdc170 and Esr1 genes correspond to the reported intergenic hormone control region (HCR) of Esr1. Different colours represent the significance of each peak (from low to high: blue, green, red). Bottom panel: Hi-C heatmaps of the WT and AF1 mutant in the Esr1 and Greb1 gene loci. The colour bar on the left of each matrix represents the signal intensity. The black arrow points to the loop of significant difference. Middle panel: virtual 4C signals at 5-kb and 2-kb resolution were obtained using sequence at 3 prime ends of the Esr1 and Greb1 domain, respectively (lower track); the corresponding hypergeomic p-values between the WT and AF1 mutant are shown above the 4C profile. The blue and orange lines of the virtual 4C plot represent WT and AF1 mutant, respectively. The black arrow points to the loop of significant difference

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