Fig. 6
Role of chromatin rearrangements in the regulation of gene transcription. a Table summarizing identified eQTLs and their intersections with interaction anchors. b Density plot showing genomic span distribution of PET clusters. d is the value (17,800 bp) by which eQTLs were split into proximal and distal. c Venn diagram showing the number of proximal (Prox) and distal eQTLs. d Enrichment/depletion of genomic elements with eQTLs. Error bars represent SD. e Enrichment/depletion of genomic elements with eQTLs of housekeeping genes. Error bars represent SD. f Abundance of gene promoters in CCDs, in which eQTLs were identified, see Fig. 2c for box plot description. n = 16 (CCDs with eQTLs in CTCF loops), 32 (CCDs with eQTLs in RNAPII loops), and 106 (CCDs with eQTLs outside loops) sample points. g Distributions of chromatin loop density in CCDs in which eQTLs were identified and in other CCDs. The density is measured for a particular CCD as an average number of CTCF-/RNAPII-mediated chromatin loops covering a 1-Mb fragment of this CCD. Differences between the groups are significant (p values < 0.001), see Fig. 2c for box plot description. n = 2125 (CCDs without eQTLs) and 142 (CCDs with eQTLs) sample points. h Linkage disequilibrium (measured as r2 value in the CEU population) between deletions shown in i and j. Colors are assigned to the deletions as in i–k. i Browser view of a 0.4-Mb genomic segment with 5 deletions identified in a part of the human population, which disrupt RNAPII anchors and are eQTLs for 6 neighboring genes (signed with the red font). Each deletion has its color. RNAPII ChIP-seq signals from 6 lymphoblastoid cells of different genotypes are presented for comparison. For each track, normalized ChIP-seq signal values were divided by the maximal value of the signal in the visualized region. Sum of the signal values over the genomic regions occupied by the deletions is marked in each signal track. H3K27ac, H3K4me3, H3K4me1, and DNase-seq signal tracks from GM12878 are shown. j Close-up on the RNAPII-mediated interactions affected by 4 of the 5 deletions. Only the loops affected by the deletions are shown for clarity. k Genes which transcription is correlated with one or more of the deletions shown in i and j (p value < 0.001). Boxes with transcription rates associated with a particular deletion are marked with the color assigned to the deletion, as in i and j, see Fig. 2c for box plot description. n = 132, 167, 146 (DEL 1); 91, 208, 146 (DEL 2); 91, 208, 146 (DEL 3); 257, 158, 30 (DEL 4); 265, 154, 26 (DEL 5) sample points. l Signal strength of histone marks and DNase hypersensitivity sites in interaction anchors intersected with proximal eQTLs, distal eQTLs, and not intersected by eQTLs. For each mark, two plots are presented. A signal track around anchor center (± 2 kb) showing values for each genomic position averaged over all anchors from a given group (top). A box plot showing mean signal values in the same regions (bottom). Original signal values represent fold change over control. CTCF and RNAPII anchors were analyzed jointly, see Fig. 2c for box plot description. n = 1000 (anchors no eQTLs), 523 (anchors distal eQTLs), and 242 (anchors prox eQTLs) sample points