About Enhancer
| Enhancer ID: | E_01_0413 |
| Species: | human |
| Position : | chr7:148805021-148807021   |
| Biosample name: | |
| Experiment class : | High+Lowthroughput |
| Enhancer type: | Enhancer |
| Disease: | Cancer |
| Pubmed ID: | 29898397 |
| Enhancer experiment: | Flow Cytometry,Histology, RNA-seq,transgenic mice |
| Enhancer experiment description: | Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8 and CD4 effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity. |
About Target gene
| Target gene : | -- |
| Strong evidence: | qRT-PCR,qPCR,ChIP,3C |
| Less strong evidence: | RNA-Seq |
| Target gene experiment description: | Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8 and CD4 effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity.;Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8 and CD4 effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity. |
About TF
| TF name : | EZH2(ENX-1,ENX1b,KMT6,KMT6A,WVS,WVS2,EZH2)FOXP3 |
| TF experiment: | Flow Cytometry,Histology, RNA-seq,transgenic mice |
| TF experiment description: | Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8 and CD4 effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity.;Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8 and CD4 effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity. |
About Function
| Enhancer function : | Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8 and CD4 effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity. |
| Enhancer function experiment: | Immunohistochemical staining |
| Enhancer function experiment description: |
Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8 and CD4 effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity. |
About SNP
| SNP ID: | -- |
Upstream Pathway Annotation of TF
| GeneName | Pathway Name | Source | Gene Number |
|---|---|---|---|
| EZH2 | Activation of anterior HOX genes in hindbrain development during early embryogenesis | reactome | 120 |
| EZH2 | Oxidative Stress Induced Senescence | reactome | 120 |
| EZH2 | PKMTs methylate histone lysines | reactome | 64 |
| EZH2 | PRC2 methylates histones and DNA | reactome | 71 |
| EZH2 | Hs_Endoderm_Differentiation_WP2853_88152 | wikipathways | 62 |
| EZH2 | Hs_Interactome_of_polycomb_repressive_complex_2_(PRC2)_WP2916_88672 | wikipathways | 15 |
| FOXP3 | Calcineurin-regulated NFAT-dependent transcription in lymphocytes | pid | 50 |
| FOXP3 | IL2 signaling events mediated by STAT5 | pid | 30 |
| FOXP3 | Hs_Allograft_Rejection_WP2328_90020 | wikipathways | 12 |
Enhancer associated network
The number on yellow line represents the distance between enhancer and
target gene