Extended Data Fig. 10: Chromosome missegregation and micronucleation promotes epigenetic dysregulation.
From: Epigenetic dysregulation from chromosomal transit in micronuclei
a, (Left) Histogram of log2 fold change of ATAC-seq counts between MMCT HCT116 cells’ clones compared to parental for chromosome of interest (COI), chromosome 1 (Chr 1; as a single chromosome control), and all other chromosomes combined (Other). KS = Kolmogorov-Smirnov test’s absolute maximum distance value between COI vs. other chromosomes. (Right) The variance of the log 2 fold change values of ATAC-seq counts of clone vs. parental control in a particular chromosome. Chromosome of interest is colored in red while chromosome 1 is colored in blue, n = 3 biological replicates. b, Analysis of clone 1 of chr 4 missegregation system in RPE-1 cells. Altered region is represented by the chromosome diagram on the top (red = altered, blue = normal). The bar plot represents the variance of log2 fold change of ATAC-seq counts (single cell-derived clones derived after transfection of p53 KO RPE-1 cells with chromosome 4 targeting sgRNA or non-targeting control) in a particular chromosome. Chromosome 1 is shown in blue (Chr 1), the whole chromosome 4 (Ch4) is shown in red, altered region of chromosome 4 is shown in gold (Ch4 ALT), and unaltered chromosome 4 region is labeled as Ch4 NORM. Left inset shows the histogram of log2 fold change of ATAC-seq counts between clone 1 compared to parental for whole chromosome 4 (red), chromosome 1 (blue) or other chromosomes (gray). Right inset shows the histogram of log2 fold change of ATAC-seq counts between clone 1 compared to parental for altered region of chromosome 4 (gold) and the unaltered region of chromosome 4 (gray). KS = Kolmogorov-Smirnov test’s absolute maximum distance value between chromosome 4 values vs. other chromosomes (left inset) or between altered chromosome 4 values vs. unaltered chromosome 4 (right inset). c, Analysis of clone 2 of chr 4 missegregation system in RPE-1 cells. Altered region is represented by the chromosome diagram on the top (red = altered, blue = normal), note that chromosome 18 is also affected due to spontaneous duplication. The bar plot represents the variance of log2 fold change of ATAC-seq counts (single cell-derived clones derived after transfection of p53 KO RPE-1 cells with chromosome 4 targeting sgRNA or non-targeting control) in a particular chromosome. Chromosome 1 is shown in blue (Chr 1), the whole chromosome 4 (Ch 4) is shown in red, altered region of chromosome 4 is shown in gold (Ch4 ALT), unaltered chromosome 4 region is labeled as Ch4 NORM, and chromosome 18 is shown in brown. Left inset shows the histogram of log2 fold change of ATAC-seq counts between clone 2 compared to parental for whole chromosome 4 (red), chromosome 1 (blue) or other chromosomes (gray). Middle inset shows the histogram of log2 fold change of ATAC-seq counts between clone 2 compared to parental for altered region of chromosome 4 (gold) and the unaltered region of chromosome 4 (gray). Right inset shows the histogram of log2 fold change of ATAC-seq counts between clone 2 compared to parental for chromosome 18 (brown), chromosome 1 (blue) or other chromosomes (gray). KS = Kolmogorov-Smirnov test’s absolute maximum distance value between chromosome 4 values vs. other chromosomes (left inset), between altered chromosome 4 values vs. unaltered chromosome 4 (middle inset), or between chromosome 18 vs. other chromosomes (right inset).
