Fig. 4: GR-bound enhancer within KCNQ1 gene regulates CDKN1C through chromatin looping. | Nature Communications

Fig. 4: GR-bound enhancer within KCNQ1 gene regulates CDKN1C through chromatin looping.

From: Glucocorticoid receptor triggers a reversible drug-tolerant dormancy state with acquired therapeutic vulnerabilities in lung cancer

Fig. 4

a (top) Hi-C contact map of A549 cell line at the resolution of 40 kb of the region surrounding CDKN1C gene (chr11:2421230-3141230). CTCF ChIP data (U01HG00790) are represented for TAD anchor sites. a (bottom left) GR ChIP sequencing data showing peaks at Enhancers 1, 2 and 3 (chr11:2799339-2801363; chr11:2846111-2848121; chr11:2880971-2882981, respectively), and CDKN1C promoter (chr11:2900697-2910745) for all the cell lines, not-treated (Veh) or treated (GC). a (bottom right) mRNA expression of CDKN1C with or without glucocorticoids (n = 2). b Normalised ChIP signal for p300 (ENCSR571KWZ), H3K27Ac (ENCSR375BQN), SMC3 (ENCSR376GQA) and Rad21 (ENCSR501UJL) at Enhancers 1, 2, 3 and CDKN1C locus in A549 cell line, untreated (Veh) or glucocorticoid-treated (GC). c CDKN1C promoter viewpoint 4 C signal across the surrounding region (chromosome 11), under the vehicle (Veh; blue) or glucocorticoid (GC; red) treatment (n = 2). P values were determined by the Wilcoxon t test. d Enhancer 1 promoter viewpoint 4 C signal across the surrounding region (chromosome 11), under the vehicle (Veh = blue) or glucocorticoid (GC = red) treatment (n = 2). P values were determined by the Wilcoxon t test. e Relative (to the geometric mean of housekeeping genes) CDKN1C mRNA expression level of vehicle (−) and GC ( + ) treated ΔCDKN1C, ΔCERES, ΔE2, ΔE3 and ΔABCB1p cell lines. Mean values ± SD depicted. Two guide RNA pairs per gene (except for ΔCDKN1C; 1 pair was used) in biological duplicates (n = 2). P values were determined by two-sided Welch’s t test. f Relative viability on GC treatment of ΔCDKN1C, ΔCERES, ΔE2, ΔE3, and ΔABCB1p cell lines. Mean values ± SD depicted. Two guide RNA pairs per genomic location (except for ΔCDKN1C; 1 pair was used) in biological quadruplicates (n = 4). P values were determined by two-sided Mann–Whitney U test.

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