About Enhancer
| Enhancer ID: | E_02_0815 |
| Species: | human |
| Position : | chr17:69541883-69542989   |
| Biosample name: | |
| Experiment class : | Low throughput |
| Enhancer type: | Enhancer |
| Disease: | Disorders of sexual development |
| Pubmed ID: | 27989796 |
| Enhancer experiment: | Luciferase Reporter Assay,PCR,Transgenic mice,Immunofluorescence |
| Enhancer experiment description: | Our previous work involving the genomic analysis of isolated DSD patients revealed a 78 kb minimal sex determining region (RevSex) far upstream of SOX9 that was duplicated in 46,XX and deleted in 46,XY DSDs. It was postulated that RevSex contains a gonadal enhancer. However, the most highly conserved sub-region within RevSex, called SR4, was neither responsive to sex determining factors in vitro nor active in the gonads of transgenic mice, suggesting that SR4 may not be functioning as a testicular enhancer. Interestingly, SR4 transgenic mice showed reporter activity in the genital tubercle, the primordium of the penis and clitoris, a previously unreported domain of Sox9 expression. SOX9 protein was detected in the genital tubercle, notably in the urethral plate epithelium, preputial glands, ventral surface ectoderm and corpus cavernosa. SR4 may therefore function as a Sox9 genital tubercle enhancer, mutations of which could possibly lead to hypospadias, a birth defect seen in the DSD patients in the RevSex study. SR4 activity and the observed SOX9 expression pattern suggest that SR4 may function as a Sox9 genital tubercle enhancer. However, conditional ablation of Sox9 in the genital tubercle using Shh-Cre/+;Sox9flox/flox mice revealed no genital tubercle abnormalities, possibly due to compensation by similar Sox factors. To conclude, we have identified a novel regulatory enhancer driving Sox9 expression during external genitalia development. |
About Target gene
| Target gene : | SOX9(CMD1,CMPD1,SRA1,SRXX2,SRXY10) |
| Strong evidence: | -- |
| Less strong evidence: | Transgenic mice,Immunofluorescence |
| Target gene experiment description: | The transcriptional activity of the SR4 enhancer in the genital tubercle led us to investigate whether SOX9 protein was also expressed there. Immunofluorescence using a SOX9 antibody on genital tubercle sections from E15.5 mouse embryos was performed (Fig. 5). SOX9 was detected in the genital tubercle of both sexes, specifically in the preputial glands, the urethral plate epithelium, ventral surface ectoderm and the corpus cavernosa. |
About TF
| TF name : | SOX9(CMD1,CMPD1,SRA1,SRXX2,SRXY10) |
| TF experiment: | Luciferase Reporter Assay |
| TF experiment description: | SR4 and TESC luciferase constructs containing an E1b minimal promoter, as well as the empty E1b-Luc vector, were transiently co-transfected into TM4 cells with expression plasmids bearing SF-1 and SRY, or SF-1 and SOX9. While activation of the TESCO enhancer was observed in luciferase assays, SR4 was not activated by the transcription factors tested. Data are represented in the form of relative luciferase activity. |
About Function
| Enhancer function : | -- |
| Enhancer function experiment: | -- |
| Enhancer function experiment description: |
-- |
About SNP
| SNP ID: | -- |
Upstream Pathway Annotation of TF
| GeneName | Pathway Name | Source | Gene Number |
|---|---|---|---|
| SOX9 | Deactivation of the beta-catenin transactivating complex | reactome | 42 |
| SOX9 | TGF_beta_Receptor | netpath | 220 |
| SOX9 | Hs_Neural_Crest_Differentiation_WP2064_79263 | wikipathways | 40 |
| SOX9 | Hs_Spinal_Cord_Injury_WP2431_87678 | wikipathways | 21 |
Enhancer associated network
The number on yellow line represents the distance between enhancer and
target gene