About Enhancer
| Enhancer ID: | E_01_286 | |
| Enhancer symbol: | -- | |
| Species: | Human | |
| Position : | chr8:27455903-27456103   |
|
| Biosample name: | HEK-293 | |
| Experiment class : | Low throughput |
| Enhancer type: | Enhancer | |
| Disease: | Alzheimer's Disease | |
| DO: | DOID:10652 | |
| Mesh: | D000544 | |
| Distance from TSS: | Intron | |
| Pubmed ID: | 28973302 |
| Enhancer experiment: | Luciferase Reporter Assay,CRISPR/Cas9,EMSA,ChIP | |
| Enhancer experiment description: | We have previously shown that the alleles at rs2279590 differentially regulate clusterin (CLU) gene expression in lens capsule tissues. This polymorphism resides in an active regulatory region marked by H3K27Ac and DNase I hypersensitive site and is an eQTL for CLU expression. Here, we report the presence of an enhancer element in surrounding region of rs2279590. Deletion of a 115 base pair intronic region flanking the rs2279590 variant through CRISPRB Cas9 genome editing in HEK293 cells demonstrated a decreased clusterin gene expression. Electrophoretic mobility shift and chromatin immunoprecipitation assays show that rs2279590 with allele “A” constitutes a transcription factor binding site for heat shock factorB1 (HSF1) but not with allele “G”. By binding to allele “A”, HSF1 abrogates the enhancer effect of the locus as validated by reporter assays. Interestingly, rs2279590 locus have a widespread enhancer effect on two nearby genes, Protein tyrosine kinase 2 beta (PTK2B) and epoxide hydrolaseB2 (EPHX2); both of which have been previously associated with AD as risk factors. |
About Target gene
| Target gene : | CLU(AAG4,APO-J,APOJ,CLI,CLU1,CLU2,KUB1,NA1/NA2,SGP-2,SGP2,SP-40,TRPM-2,TRPM2),EPHX2(ABHD20,CEH,SEH),PTK2B(CADTK,CAKB,FADK2,FAK2,PKB,PTK,PYK2,RAFTK) | |
| Strong evidence: | CRISPR/Cas9 | |
| Less strong evidence: | Luciferase Reporter Assay,EMSA,ChIP | |
| Target gene experiment description: | We have previously shown that the alleles at rs2279590 differentially regulate clusterin (CLU) gene expression in lens capsule tissues. This polymorphism resides in an active regulatory region marked by H3K27Ac and DNase I hypersensitive site and is an eQTL for CLU expression. Here, we report the presence of an enhancer element in surrounding region of rs2279590. Deletion of a 115 base pair intronic region flanking the rs2279590 variant through CRISPRB Cas9 genome editing in HEK293 cells demonstrated a decreased clusterin gene expression. Electrophoretic mobility shift and chromatin immunoprecipitation assays show that rs2279590 with allele “A” constitutes a transcription factor binding site for heat shock factorB1 (HSF1) but not with allele “G”. By binding to allele “A”, HSF1 abrogates the enhancer effect of the locus as validated by reporter assays. Interestingly, rs2279590 locus have a widespread enhancer effect on two nearby genes, Protein tyrosine kinase 2 beta (PTK2B) and epoxide hydrolaseB2 (EPHX2); both of which have been previously associated with AD as risk factors. |
About TF
| TF name : | HSF1(HSTF1) | |
| TF experiment: | EMSA,ChIP | |
| TF experiment description: | Electrophoretic mobility shift and chromatin immunoprecipitation assays show that rs2279590 with allele "A"constitutes a transcription factor binding site for heat shock factor-1 (HSF1) but not with allele “G”.By binding to allele “A”, HSF1 abrogates the Enhancer effect of the locus as validated by reporter assays. |
About Function
| Enhancer function : | -- |
| Enhancer function experiment: | -- |
| Enhancer function experiment description: |
-- |
About SNP
| SNP ID: | rs2279590 | |
| SNP position: | 27456253 |
| SNP experiment: | EMSA,ChIP |
Enhancer associated network
The number on yellow line represents the distance between enhancer and target gene
