About Enhancer
| Enhancer ID: | E_01_0421 |
| Species: | human |
| Position : | chr1:55036580-55038580   |
| Biosample name: | |
| Experiment class : | High+Lowthroughput |
| Enhancer type: | Enhancer |
| Disease: | Cancer |
| Pubmed ID: | 29885262 |
| Enhancer experiment: | transcription,luciferase assay,Western blot,RT-qPCR,ELISA,ChIP, |
| Enhancer experiment description: | We, therefore, studied the effect of PCSK9 on interferon (IFN) ? expression. We show that PCSK9 decreases IFN? promoter/enhancer activity, mRNA and protein levels, and its downstream 2',5'-oligoadenylate synthetase-1 mRNA level. ProPCSK9, but not the cleaved PCSK9, down-regulates IFN? promoter/enhancer activity. Moreover, PCSK9 decreases IFN? promoter/enhancer activity through the positive regulatory domain IV region where the activating transcription factor-2 (ATF-2)/c-Jun heterodimer binds. Mechanistically, we demonstrate an interaction between PCSK9 and ATF-2, which reduces ATF-2/c-Jun dimerization and ATF-2/c-Jun binding to the IFN? enhancer. This novel function of PCSK9 should have important implications in optimizing the clinical use of PCSK9 inhibitors. |
About Target gene
| Target gene : | PCSK9 |
| Strong evidence: | qRT-PCR,qPCR,ChIP,3C |
| Less strong evidence: | RNA-Seq |
| Target gene experiment description: | We, therefore, studied the effect of PCSK9 on interferon (IFN) ? expression. We show that PCSK9 decreases IFN? promoter/enhancer activity, mRNA and protein levels, and its downstream 2',5'-oligoadenylate synthetase-1 mRNA level. ProPCSK9, but not the cleaved PCSK9, down-regulates IFN? promoter/enhancer activity. Moreover, PCSK9 decreases IFN? promoter/enhancer activity through the positive regulatory domain IV region where the activating transcription factor-2 (ATF-2)/c-Jun heterodimer binds. Mechanistically, we demonstrate an interaction between PCSK9 and ATF-2, which reduces ATF-2/c-Jun dimerization and ATF-2/c-Jun binding to the IFN? enhancer. This novel function of PCSK9 should have important implications in optimizing the clinical use of PCSK9 inhibitors. |
About TF
| TF name : | -- |
| TF experiment: | transcription,luciferase assay,Western blot,RT-qPCR,ELISA,ChIP, |
| TF experiment description: | We, therefore, studied the effect of PCSK9 on interferon (IFN) ? expression. We show that PCSK9 decreases IFN? promoter/enhancer activity, mRNA and protein levels, and its downstream 2',5'-oligoadenylate synthetase-1 mRNA level. ProPCSK9, but not the cleaved PCSK9, down-regulates IFN? promoter/enhancer activity. Moreover, PCSK9 decreases IFN? promoter/enhancer activity through the positive regulatory domain IV region where the activating transcription factor-2 (ATF-2)/c-Jun heterodimer binds. Mechanistically, we demonstrate an interaction between PCSK9 and ATF-2, which reduces ATF-2/c-Jun dimerization and ATF-2/c-Jun binding to the IFN? enhancer. This novel function of PCSK9 should have important implications in optimizing the clinical use of PCSK9 inhibitors. |
About Function
| Enhancer function : | We, therefore, studied the effect of PCSK9 on interferon (IFN) ? expression. We show that PCSK9 decreases IFN? promoter/enhancer activity, mRNA and protein levels, and its downstream 2',5'-oligoadenylate synthetase-1 mRNA level. ProPCSK9, but not the cleaved PCSK9, down-regulates IFN? promoter/enhancer activity. Moreover, PCSK9 decreases IFN? promoter/enhancer activity through the positive regulatory domain IV region where the activating transcription factor-2 (ATF-2)/c-Jun heterodimer binds. Mechanistically, we demonstrate an interaction between PCSK9 and ATF-2, which reduces ATF-2/c-Jun dimerization and ATF-2/c-Jun binding to the IFN? enhancer. This novel function of PCSK9 should have important implications in optimizing the clinical use of PCSK9 inhibitors. |
| Enhancer function experiment: | Immunohistochemical staining |
| Enhancer function experiment description: |
We, therefore, studied the effect of PCSK9 on interferon (IFN) ? expression. We show that PCSK9 decreases IFN? promoter/enhancer activity, mRNA and protein levels, and its downstream 2',5'-oligoadenylate synthetase-1 mRNA level. ProPCSK9, but not the cleaved PCSK9, down-regulates IFN? promoter/enhancer activity. Moreover, PCSK9 decreases IFN? promoter/enhancer activity through the positive regulatory domain IV region where the activating transcription factor-2 (ATF-2)/c-Jun heterodimer binds. Mechanistically, we demonstrate an interaction between PCSK9 and ATF-2, which reduces ATF-2/c-Jun dimerization and ATF-2/c-Jun binding to the IFN? enhancer. This novel function of PCSK9 should have important implications in optimizing the clinical use of PCSK9 inhibitors. |
About SNP
| SNP ID: | -- |
Upstream Pathway Annotation of TF
| GeneName | Pathway Name | Source | Gene Number |
|---|
Enhancer associated network
The number on yellow line represents the distance between enhancer and
target gene