Fig. 5: Human-specific CTCF loops at the BLK locus govern enhancer-promoter interactions, contributing to systemic lupus erythematosus (SLE) susceptibility.

a Human-specific CTCF loops encompass the BLK locus, originating from a human-specific CTCF site in B-lymphoblastoid cells. Dashed red lines indicate the human-specific CTCF site and its corresponding positions in non-human primates. b DNA sequence alignment of the human-specific CTCF site, with human-specific single-nucleotide substitutions highlighted. The insertion variant rs558245864 (C > CG) is marked. c Regional association plot showing rs558245864 and its linkage to GWAS single-nucleotide polymorphisms (SNPs) for SLE susceptibility. The surrounding SNPs of rs558245864 are colored according to their degree of linkage disequilibrium (r²) with rs558245864. P values for r² (shown on left y-axis) were calculated using chi-square test with 1 degree of freedom. Recombination rates are shown in the sky-blue curve. d Visualization of RNAPII loops at the BLK locus from human (GM12878) and macaque B-lymphoblastoid cells. CTCF loops for GM12878 in the same region are shown in (a, see “Human”). Dashed red lines indicate the human-specific CTCF site and its corresponding position in macaques. The BLK promoter and the human-specific enhancer (HSE) are highlighted in yellow and blue, respectively. e Contact maps at a 1-kb resolution representing combined CTCF- and RNAPII-mediated chromatin interactions in B-lymphoblastoid cells from individuals GM12878 (top) and HG00514 (bottom) at the BLK locus. The red pentagon labeled with “B” marks the human-specific CTCF site. The genotypes at the CTCF site corresponding to each individual are shown in parentheses beside their IDs. The blue and green boxes indicate the reduced and increased chromatin interactions in HG00514 compared to GM12878, respectively. f BLK transcript levels in B-lymphoblastoid cells from individuals with different genotypes at the rs558245864 variant. In the box plots, the central line indicates the median, the box spans the interquartile range, and the whiskers extend to 1.5× the interquartile range. P values are provided (one-tailed Wilcoxon test). g BLK transcript levels in B lymphocytes from a healthy individual (C/C) and SLE patients (C/CG or CG/CG) with rs558245864. Data shown as mean ± standard deviation. P values are provided (one-tailed Student's t-test). The source data, n numbers, and exact P values for (f) and (g) are provided in the Source Data file.