Extended Data Fig. 9: UTX condensates regulate long-range chromatin interactions. | Nature

Extended Data Fig. 9: UTX condensates regulate long-range chromatin interactions.

From: UTX condensation underlies its tumour-suppressive activity

Extended Data Fig. 9

a. Distribution of types of genomic interactions. P, promoter (TSS ± 2kb); E, enhancer (promoter non-overlapped, union DNase I hypersensitive sites); Desert: all other interactions, <1% in all. b. Distribution of the chromatin loop size in indicated cells. A loop is the connection of two different 5 kb chromatin regions by high-confidence contact reads. c. Number of chromatin loops identified in indicated cells. For simplicity, Venn diagrams for only Vector, WT, and ΔcIDR cells are shown. d. Box plots for the number of normalized HiChIP reads per loop for identified loops in indicated cells. The normalized read counts in a loop represents the relative intensity of the interaction. For H3K4me3 HiChIP (left), n = 57632, 67755, 88993, 95696, 90566 loops in Vector, WT, ΔcIDR, UTX-eIFIDR, ΔcTPR samples, respectively. For H3K27ac HiChIP (right), n = 20912, 27794, 37811, 31232, 26556 loops in Vector, WT, ΔcIDR, UTX-eIFIDR, ΔcTPR samples, respectively. e. Scatter plots for all 26,237 genes using the promoter H3K27ac HiChIP DCI of cells indicated on the x and y axes. Dashed line shows the linear fit with indicated correlation coefficient (r). Red and blue dots represent 479 and 112 genes with DCI of WT over vector > 5 and < −5, respectively. f. Box plots for DCI scores comparing cells indicated on x axis for genes represented by the red (left) and blue (right) dots from e. P values are shown for data significantly greater or less than 0 by two-sided one sample t-test. Left, n = 479 genes each; right, n = 112 genes each. g. Box plots for DCI scores at promoter (TSS ± 2kb) of cell samples (indicated on top of each plot) for genes whose expression was up- or downregulated (indicated on x axis) in the corresponding cells (indicated on top of each plot). Genes were selected as those both have expression and DCI data. The trend of change and the P value between indicated two groups of genes are shown. n = indicated number on x axis. h. Gene pathway analysis using DCI scores from indicated HiChIP data. Red shows pathways relevant to cancer or leukaemia inhibition among the top 20 significantly enriched Biological Processes for genes with promoter chromatin interactions substantially increased in WT over vector expressing cells. Blue shows pathways particularly relevant to cell growth and survival among the top 20 significantly enriched Biological Processes for genes with promoter chromatin interactions substantially decreased in WT over vector expressing cells. All by Metascape. Details in Supplementary Table 5. i, j. BART3D results showing transcriptional regulators that were likely to be associated with genomic regions that had increased (i) or decreased (j) chromatin interactions in WT over vector expressing cells from indicated HiChIP datasets. Top 10 ranked transcriptional regulators are labeled in red and their names are shown. For all box plots, data are median (horizontal line), 25–75th percentiles (box) and 1.5 times the interquartile range recorded (whiskers). P values by two-sided t-test for all except by hypergeometric test for h, and from BART3D for i, j.

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