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Fig. 3 | Epigenetics & Chromatin

Fig. 3

From: Multiple distinct domains of human XIST are required to coordinate gene silencing and subsequent heterochromatin formation

Fig. 3

The role of chromatin modification on XIST-induced gene silencing. A The ability of Full XIST to induce allele-specific repression at four distal genes is shown when cells were treated with chemical inhibitors for XIST-associated chromatin remodelers. Three biological replicates were tested for each condition shown and statistical significance of a treatment’s effect on XIST-induced silencing was calculated using a t-test with multiple testing correction. The concentration of chemical inhibitors in media along with the factor inhibited are listed, and the key for the genes assessed is beside panel B. B Test of whether HDACs contribute to silencing if used at much higher concentrations for only 2 days, as longer exposure was lethal to cells. Strength of silencing for these higher HDACi treatments was normalized and compared to uninhibited 2ddox Full XIST by t-test. C Example images depicting XIST (green) mediated formation of a transcriptionally inert domain (Cot-1, red) over the course of five days of induction combined with chemical inhibition. D Boxplot showing distribution of Cot-1 depletion (z-score s) across populations of 60 cells, following 5 days of chemical inhibition and Full XIST induction. All conditions were blinded through the process and statistical comparisons of population distributions of z-score s performed using the Mann–Whitney test. AD Chemical inhibition was performed using the following: TSA (HDACi), RGPF966 (HDAC3i), ryuvidine (KMT5A), GSK343 (PRC2i) and PRT4165 (PRC1i). The thresholds for statistical significance were all corrected for multiple testing correction from * < 0.05, ** < 0.01, *** < 0.001 (p values listed individually in Additional file 1: Table S5)

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