Fig. 4.

A single-nucleotide polymorphism (SNP; rs1801311) at schizophrenia risk locus 22q13.2 disrupts binding of three transcription factors (TFs). a SNP rs1801311 is located in the binding motif of POLR2A, TAF1 and YY1 TFs, and disrupts occupied POLR2A, TAF1 and YY1 binding site in human brain tissues or neuronal cell lines. Position weight matrices (PWMs) of corresponding TFs and the location of rs1801311 are shown (with red dotted box). b Genomic region (1 kb) surrounding SNP rs1801311 is shown with three featured visualization tracks, including DNase-Seq signal (light blue), chromatin immunoprecipitation and sequencing (ChIP-Seq) signal (green) for the selected TF and histone modifications (purple). The heights of the colored graphs (in b) reflect the ChIP-Seq and DNase-Seq signal intensities, which were scaled from 0 to 50 (signal intensities larger than 50 were truncated and not shown). The location of rs1801311 is highlighted with the dotted red line. c–e Reporter gene assays showed that the allelic differences at the rs1801311 influenced the luciferase activity significantly in HEK293 cells (c), SK-N-SH cells (d) and SH-SY5Y cells (e). Of note, the A allele of rs1801311 conferred a significant higher activity compared with G allele in all three tested cell lines. Data represent mean ± SD; n = 8 for each group in c HEK293 cells; n = 16 for each group in d SK-N-SH cells and e SH-SY5Y cells. ***P < 0.001, two-tailed Student’s t-test. Source data are provided as a Source Data file