About Enhancer
| Enhancer ID: | E_01_284 | |
| Enhancer symbol: | rs6758183 enhancer | |
| Species: | Human | |
| Position : | chr2:226998914-227004586   |
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| Biosample name: | Human Corneal Epithelial Cells | |
| Experiment class : | Low+High throughput |
| Enhancer type: | Enhancer | |
| Disease: | -- | |
| DO: | -- | |
| Mesh: | -- | |
| Distance from TSS: | >2KB | |
| Pubmed ID: | 28916725 |
| Enhancer experiment: | Luciferase Reporter Assay,ChIP-seq | |
| Enhancer experiment description: | Because of their importance in controlling cell type–specific gene expression, we also defined SEs, using the strength of the H3K27ac mark as described previously (5, 6). We identified 1154 SEs and 12,424 TEs in corneal epithelial cells as well as 76,205 distal regulatory regions, marked by H3K4me1 alone (Fig. 1A). As expected, the majority of enhancers was found at distal sites in the genome rather than in proximal promoters (Fig. 1B). Although TEs showed a trend toward being localized near genes, SEs were even more strongly enriched near genes; most SEs were found within 50 kb of a transcriptional start site.Together, these data indicate that most epithelial distal regulatory regions are common to multiple epithelial cell types, differing only in the type of enhancer and/or the level of enhancer activity, as indicated by the activation mark H3K27Ac (Fig. 2C). |
About Target gene
| Target gene : | IRS1(HIRS-1) | |
| Strong evidence: | -- | |
| Less strong evidence: | ChIA-PET | |
| Target gene experiment description: | As insulin signaling is important for growth and development of both the corneal epithelium and the stroma, IRS1 is a candidate target for the enhancer containing rs6758183. Consistent with this possibility, in previously published siRNA data for EHF in corneal epithelial cells, we found that knockdown of EHF caused a small but significant increase in IRS1 gene expression (Figure 7G) (18). Together, these data suggest EHF regulates IRS1 through binding to the rs6758183 enhancer and that disruption of the EHF motif causes reduced affinity of EHF for this site, resulting in aberrant IRS1 expression during corneal development. |
About TF
| TF name : | EHF(ESE3,ESE3B,ESEJ) | |
| TF experiment: | ChIP,siRNA | |
| TF experiment description: | We hypothesized that these SNP variants could disrupt transcription factor binding, altering enhancer activity for each allele. At rs6758183, the disease associated A allele increased the strength of a SMAD motif, and decreased the strength of an ETS motif (Figure 7D). Using ChIP, we found that EHF bound to the WT allele of rs6758183, suggesting disruption of EHF binding by the SNP could result in the observed differences in enhancer activity (Figure 7F). Intriguingly, the WT version of the SNP showed less enhancer activity than the mutant, suggesting EHF binding acts to repress the enhancer region. When this binding is lost, the enhancer becomes overactive, a change that could result in growth imbalances that cause alterations in the curvature and refractive power of the cornea. Consistent with this possibility, in previously published siRNA data for EHF in corneal epithelial cells, we found that knockdown of EHF caused a small but significant increase in IRS1 gene expression (Figure 7G) (18). Together, these data suggest EHF regulates IRS1 through binding to the rs6758183 enhancer and that disruption of the EHF motif causes reduced affinity of EHF for this site, resulting in aberrant IRS1 expression during corneal development. |
About Function
| Enhancer function : | -- |
| Enhancer function experiment: | -- |
| Enhancer function experiment description: |
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About SNP
| SNP ID: | rs6758183 | |
| SNP position: | 226136270 |
| SNP experiment: | Luciferase Reporter Assay |
Enhancer associated network
The number on yellow line represents the distance between enhancer and target gene
