About Enhancer
| Enhancer ID: | E_01_196 | |
| Enhancer symbol: | -- | |
| Species: | Human | |
| Position : | chr12:98559923-98563615   |
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| Biosample name: | Induced Pluripotent Stem Cells | |
| Experiment class : | Low+High throughput |
| Enhancer type: | Enhancer | |
| Disease: | Schizophrenia | |
| DO: | DOID:5419 | |
| Mesh: | D012559 | |
| Distance from TSS: | >2KB | |
| Pubmed ID: | 25453756 |
| Enhancer experiment: | 3C,Luciferase Reporter Assay | |
| Enhancer experiment description: | We identified 4 SNPs (rs2159100, rs12315711, rs11062170, rs4765905) that are in perfect LD with rs758170 and rs1006737, and lie within two predicted enhancers (spanning 1.4Kb and 1.85Kb), ∼185Kb downstream from the gene’s TSS (Figure 5A, Figure 5B). To identify whether the predicted enhancer region might be capable of forming promoter–enhancer loops, we mapped its physical interaction with the CACNA1C TSS in human dorsolateral prefrontal cortex (n = 6) and hiPSC derived-neurons by chromosome conformation capture (3C) assay. Of the 17 restriction site regions tested, only one displayed an increased interaction with the TSS in human postmortem tissue (Primer #4 in Figure 5A–D). This enhancer region includes rs2159100 (MAF = 0.35, GWAS P value = 1.1 × 10−10) and rs12315711 (MAF=0.35, GWAS P value = 1.1 × 10−10) and demonstrates increased interaction frequency with the CACNA1C promoter (F (16, 83) = 5.52, P = 8 × 10−8). In addition to being in an enhancer region, rs2159100 also co-localizes with a 600bp DHS region. Thus, we examined its effect on transcriptional activity in in vitro experiments. Compared to the reference rs2159100 C allele, the risk T variant is associated with decreased transcriptional activity in HEK-293 and Neuro-2a cells (42% (P < 0.0001) and 23% (P < 0.05) reduction in luciferase activity, respectively) (Figure 5E). |
About Target gene
| Target gene : | CACNA1C (CACH2,CACN2,CACNL1A1,CCHL1A1,CaV1.2,LQT8,TS,TS.LQT8) | |
| Strong evidence: | 3C | |
| Less strong evidence: | Luciferase Reporter Assay | |
| Target gene experiment description: | We identified 4 SNPs (rs2159100, rs12315711, rs11062170, rs4765905) that are in perfect LD with rs758170 and rs1006737, and lie within two predicted enhancers (spanning 1.4Kb and 1.85Kb), ∼185Kb downstream from the gene’s TSS (Figure 5A, Figure 5B). To identify whether the predicted enhancer region might be capable of forming promoter–enhancer loops, we mapped its physical interaction with the CACNA1C TSS in human dorsolateral prefrontal cortex (n = 6) and hiPSC derived-neurons by chromosome conformation capture (3C) assay. Of the 17 restriction site regions tested, only one displayed an increased interaction with the TSS in human postmortem tissue (Primer #4 in Figure 5A–D). This enhancer region includes rs2159100 (MAF = 0.35, GWAS P value = 1.1 × 10−10) and rs12315711 (MAF=0.35, GWAS P value = 1.1 × 10−10) and demonstrates increased interaction frequency with the CACNA1C promoter (F (16, 83) = 5.52, P = 8 × 10−8). In addition to being in an enhancer region, rs2159100 also co-localizes with a 600bp DHS region. Thus, we examined its effect on transcriptional activity in in vitro experiments. Compared to the reference rs2159100 C allele, the risk T variant is associated with decreased transcriptional activity in HEK-293 and Neuro-2a cells (42% (P < 0.0001) and 23% (P < 0.05) reduction in luciferase activity, respectively) (Figure 5E). |
About TF
| TF name : | -- | |
| TF experiment: | -- | |
| TF experiment description: | -- |
About Function
| Enhancer function : | -- |
| Enhancer function experiment: | -- |
| Enhancer function experiment description: |
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About SNP
| SNP ID: | -- | |
| SNP position: | -- |
| SNP experiment: | -- |
Enhancer associated network
The number on yellow line represents the distance between enhancer and target gene
