| Enhancer ID: | E_02_0752 |
| Species: | human |
| Position : | chr1:47704791-47705107 |
| Biosample name: | |
| Experiment class : | Low throughput |
| Enhancer type: | Super-Enhancer |
| Disease: | Central nervous system leukemia |
| Pubmed ID: | 30518632 |
| Enhancer experiment: | ChIP-qPCR,qRT-PCR,ChIP,Transgenic mice |
| Enhancer experiment description: | We found robust cytotoxicity against T-ALL cells, but not normal bone marrow progenitors, for two N-alkylated TCP derivatives, S2116 and S2157. The two compounds induced apoptosis in TCP-resistant T-ALL cells in vitro and in vivo by repressing transcription of the NOTCH3 and TAL1 genes through increased H3K9 methylation and reciprocal H3K27 deacetylation at super-enhancer regions. |
| Target gene : | TAL1(SCL,TCL5,bHLHa17,tal-1),TAL1(SCL,TCL5,bHLHa17,tal-1),TAL1(SCL,TCL5,bHLHa17,tal-1) |
| Strong evidence: | -- |
| Less strong evidence: | qRT-PCR,ChIP |
| Target gene experiment description: | we found that both S2116 and S2157 readily increased the methylation level of H3K9 and reciprocally reduced the acetylation level of H3K27 at Super-Enhancer regions of the NOTCH3 and TAL1 genes (GRCh38/hg38: 15,198,031-15,197,862 and GRCh38/hg38: 47,239,435-47,239,119,respectively) using ChIP assays.In addition,global ChIP-seq analyses revealed that the acetylation level of H3K27 was readily decreased by LSD1 inhibition through the entire range of NOTCH3 and TAL1 Enhancers.;we found that both S2116 and S2157 readily increased the methylation level of H3K9 and reciprocally reduced the acetylation level of H3K27 at Super-Enhancer regions of the NOTCH3 and TAL1 genes (GRCh38/hg38: 15,198,031-15,197,862 and GRCh38/hg38: 47,239,435-47,239,119,respectively) using ChIP assays.In addition,global ChIP-seq analyses revealed that the acetylation level of H3K27 was readily decreased by LSD1 inhibition through the entire range of NOTCH3 and TAL1 Enhancers.;we found that both S2116 and S2157 readily increased the methylation level of H3K9 and reciprocally reduced the acetylation level of H3K27 at Super-Enhancer regions of the NOTCH3 and TAL1 genes (GRCh38/hg38: 15,198,031-15,197,862 and GRCh38/hg38: 47,239,435-47,239,119,respectively) using ChIP assays.In addition,global ChIP-seq analyses revealed that the acetylation level of H3K27 was readily decreased by LSD1 inhibition through the entire range of NOTCH3 and TAL1 Enhancers. |
| TF name : | ZEB2(HSPC082,SIP-1,SIP1,SMADIP1,ZFHX1B)ZEB2(HSPC082,SIP-1,SIP1,SMADIP1,ZFHX1B)ZEB2(HSPC082,SIP-1,SIP1,SMADIP1,ZFHX1B) |
| TF experiment: | RT-PCR |
| TF experiment description: | We used the Expression Assays(Hs01097987 for TAL1, Hs01128537 for NOTCH3, Hs00207691 for ZEB2, and Hs01922876 forGAPDH) and TaqMan Universal PCR Master Mix (Applied Biosystems, Waltham, MA) for real-time quantitative RT-PCR (RQ-PCR).;We used the Expression Assays(Hs01097987 for TAL1, Hs01128537 for NOTCH3, Hs00207691 for ZEB2, and Hs01922876 forGAPDH) and TaqMan Universal PCR Master Mix (Applied Biosystems, Waltham, MA) for real-time quantitative RT-PCR (RQ-PCR).;We used the Expression Assays(Hs01097987 for TAL1, Hs01128537 for NOTCH3, Hs00207691 for ZEB2, and Hs01922876 forGAPDH) and TaqMan Universal PCR Master Mix (Applied Biosystems, Waltham, MA) for real-time quantitative RT-PCR (RQ-PCR). |
| Enhancer function : | -- |
| Enhancer function experiment: | -- |
| Enhancer function experiment description: |
-- |
| SNP ID: | -- |
| GeneName | Pathway Name | Source | Gene Number |
|---|---|---|---|
| ZEB2 | TGF_beta_Receptor | netpath | 220 |
| ZEB2 | TGF_beta_Receptor | netpath | 220 |
| ZEB2 | TGF_beta_Receptor | netpath | 220 |