0000000001302263
AUTHOR
Jan Krefting
Evolutionary stability of topologically associating domains is associated with conserved gene regulation
AbstractBackgroundThe human genome is highly organized in the three-dimensional nucleus. Chromosomes fold locally into topologically associating domains (TADs) defined by increased intra-domain chromatin contacts. TADs contribute to gene regulation by restricting chromatin interactions of regulatory sequences, such as enhancers, with their target genes. Disruption of TADs can result in altered gene expression and is associated to genetic diseases and cancers. However, it is not clear to which extent TAD regions are conserved in evolution and whether disruption of TADs by evolutionary rearrangements can alter gene expression.ResultsHere, we hypothesize that TADs represent essential functiona…
Additional file 3: of Evolutionary stability of topologically associating domains is associated with conserved gene regulation
Figure S3. Distance between rearrangement breakpoints and random controls to closest TAD boundary. For each species (y-axis) and fill size threshold (vertical panels) the distances from all identified rearrangement breakpoints to its closest TAD boundary (x-axis) are compared between actual rearrangements (blue) and 100 times randomized background controls (gray). The left panel shows distances to next hESC TAD boundary and the right panel distances to closest GM12878 contact domain boundary. P-values according to Wilcoxonâ s rank-sum test. (PDF 14 kb)
Additional file 2: of Evolutionary stability of topologically associating domains is associated with conserved gene regulation
Figure S2. Distribution of evolutionary rearrangement breakpoints between human and 12 vertebrate genomes around domains. Relative breakpoint numbers from human and different species (horizontal panels) around hESC TADs (left), GM12878 contact domains (center), and GRBs (left). Blue color scale represents breakpoints from different fill-size thresholds. Dotted lines in gray show simulated background controls of randomly placed breakpoints. (PDF 42 kb)
Additional file 1: of Evolutionary stability of topologically associating domains is associated with conserved gene regulation
Figure S1. Breakpoint identification accuracy as compared to gene synteny. Considered are adjacent pairs of human genes with one-to-one orthologs and intergenic distance below a size threshold. (A) Positive predicted value as the fraction of non-syntenic gene pairs with breakpoint from all considered gene pairs (syntenic and non-syntenic) with breakpoint. (B) False positive rate as the percent of syntenic gene pairs with breakpoint from the sum of syntenic pairs with breakpoint and non-syntenic gene pairs without breakpoint. (PDF 21 kb)
Additional file 4: of Evolutionary stability of topologically associating domains is associated with conserved gene regulation
Table S1. Matching tissues and samples with CAGE expression data in human and mouse. (TSV 2 kb)
Additional file 5: of Evolutionary stability of topologically associating domains is associated with conserved gene regulation
Table S2. Ortholog genes in human and mouse with gene expression correlation across tissues. (TSV 1036 kb)