About Enhancer

Enhancer ID: E_01_0475
Species: human
Position : chr1:186669486-186671486
Biosample name:
Experiment class : High+Lowthroughput
Enhancer type: Enhancer
Disease: Inflammation, rheumatoid arthritis (ra)
Pubmed ID:  29768212
Enhancer experiment: Immunohistochemistry,Western Blot,qPCR,ELISA,EMSA,siRNA-Mediated Knockdown,Immunofluorescence Staining,Automated Imaging
Enhancer experiment description: mTOR pathway activation is associated with decreased NF-?B-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA).

About Target gene

Target gene : CXCL11,TNFSF13B
Strong evidence: qRT-PCR,qPCR,ChIP,3C
Less strong evidence: RNA-Seq
Target gene experiment description: mTOR pathway activation is associated with decreased NF-?B-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA).;mTOR pathway activation is associated with decreased NF-?B-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA).;mTOR pathway activation is associated with decreased NF-?B-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA).;mTOR pathway activation is associated with decreased NF-?B-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA).

About TF

TF name : PTGS2STAT1(CANDF7,IMD31A,IMD31B,IMD31C,ISGF-3,STAT91)
TF experiment: Immunohistochemistry,Western Blot,qPCR,ELISA,EMSA,siRNA-Mediated Knockdown,Immunofluorescence Staining,Automated Imaging
TF experiment description: mTOR pathway activation is associated with decreased NF-?B-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA).;mTOR pathway activation is associated with decreased NF-?B-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA).;mTOR pathway activation is associated with decreased NF-?B-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA).;mTOR pathway activation is associated with decreased NF-?B-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA).

About Function

Enhancer function : mTOR pathway activation is associated with decreased NF-?B-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA).
Enhancer function experiment: Immunohistochemical staining
Enhancer function
experiment description:		 mTOR pathway activation is associated with decreased NF-?B-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA).

About SNP

SNP ID: --

Upstream Pathway Annotation of TF

GeneName Pathway Name Source Gene Number
PTGS2 Acetaminophen Action Pathway smpdb 28
PTGS2 Acetylsalicylic Acid Action Pathway smpdb 28
PTGS2 Antipyrine Action Pathway smpdb 28
PTGS2 Antrafenine Action Pathway smpdb 28
PTGS2 Arachidonic Acid Metabolism smpdb 28
PTGS2 Bromfenac Action Pathway smpdb 28
PTGS2 C-MYB transcription factor network pid 87
PTGS2 C20 prostanoid biosynthesis humancyc 9
PTGS2 Calcineurin-regulated NFAT-dependent transcription in lymphocytes pid 50
PTGS2 Calcium signaling in the CD4+ TCR pathway pid 29
PTGS2 Carprofen Action Pathway smpdb 28
PTGS2 Celecoxib Action Pathway smpdb 34
PTGS2 Celecoxib Metabolism Pathway smpdb 8
PTGS2 Diclofenac Action Pathway smpdb 28
PTGS2 Diflunisal Action Pathway smpdb 28
PTGS2 Etodolac Action Pathway smpdb 28
PTGS2 Etoposide Action Pathway smpdb 18
PTGS2 Etoposide Metabolism Pathway smpdb 18
PTGS2 Etoricoxib Action Pathway smpdb 28
PTGS2 Fenoprofen Action Pathway smpdb 28
PTGS2 Flurbiprofen Action Pathway smpdb 28
PTGS2 Ibuprofen Action Pathway smpdb 47
PTGS2 Ibuprofen Metabolism Pathway smpdb 22
PTGS2 Indomethacin Action Pathway smpdb 29
PTGS2 Inflammation mediated by chemokine and cytokine signaling pathway panther 189
PTGS2 Ketoprofen Action Pathway smpdb 28
PTGS2 Ketorolac Action Pathway smpdb 28
PTGS2 Leukotriene C4 Synthesis Deficiency smpdb 28
PTGS2 Lornoxicam Action Pathway smpdb 28
PTGS2 Lumiracoxib Action Pathway smpdb 28
PTGS2 Magnesium salicylate Action Pathway smpdb 28
PTGS2 Mefenamic Acid Action Pathway smpdb 28
PTGS2 Meloxicam Action Pathway smpdb 28
PTGS2 Nabumetone Action Pathway smpdb 28
PTGS2 Naproxen Action Pathway smpdb 28
PTGS2 Nepafenac Action Pathway smpdb 28
PTGS2 Nicotinamide salvaging reactome 8
PTGS2 Oxaprozin Action Pathway smpdb 28
PTGS2 Phenylbutazone Action Pathway smpdb 28
PTGS2 Piroxicam Action Pathway smpdb 28
PTGS2 Prostaglandin and Leukotriene metabolism ( Prostaglandin and Leukotriene metabolism ) inoh 22
PTGS2 Rofecoxib Action Pathway smpdb 28
PTGS2 S1P1 pathway pid 20
PTGS2 Salicylate-sodium Action Pathway smpdb 28
PTGS2 Salicylic Acid Action Pathway smpdb 28
PTGS2 Salsalate Action Pathway smpdb 28
PTGS2 Signaling mediated by p38-alpha and p38-beta pid 35
PTGS2 Sulindac Action Pathway smpdb 28
PTGS2 Suprofen Action Pathway smpdb 28
PTGS2 Synthesis of 15-eicosatetraenoic acid derivatives reactome 6
PTGS2 Synthesis of Prostaglandins (PG) and Thromboxanes (TX) reactome 14
PTGS2 Tenoxicam Action Pathway smpdb 28
PTGS2 Tiaprofenic Acid Action Pathway smpdb 28
PTGS2 Tolmetin Action Pathway smpdb 28
PTGS2 Trisalicylate-choline Action Pathway smpdb 28
PTGS2 Valdecoxib Action Pathway smpdb 28
PTGS2 untitled panther 64
PTGS2 Arachidonic acid metabolism kegg 57
PTGS2 VEGF signaling pathway kegg 70
PTGS2 Leishmaniasis kegg 71
PTGS2 Pathways in cancer kegg 321
PTGS2 Small cell lung cancer kegg 83
PTGS2 Hs_VEGFA-VEGFR2_Signaling_Pathway_WP3888_90000 wikipathways 153
PTGS2 Hs_Aryl_Hydrocarbon_Receptor_WP2586_91687 wikipathways 16
PTGS2 Hs_Selenium_Micronutrient_Network_WP15_88908 wikipathways 35
STAT1 Angiogenesis panther 141
STAT1 BCR netpath 161
STAT1 CXCR4-mediated signaling events pid 87
STAT1 Downstream signal transduction reactome 29
STAT1 EGF receptor signaling pathway panther 109
STAT1 EGFR1 netpath 475
STAT1 EPO signaling pathway pid 33
STAT1 EPO signaling pathway(JAK2 STAT1 STAT3 STAT5) ( EPO signaling pathway(JAK2 STAT1 STAT3 STAT5) ) inoh 12
STAT1 ErbB1 downstream signaling pid 105
STAT1 FGF signaling pathway pid 55
STAT1 Gene expression of SOCS by STAT dimer ( JAK-STAT pathway and regulation pathway Diagram ) inoh 14
STAT1 Gene expression of SOCS1 by STAT dimer ( JAK-STAT pathway and regulation pathway Diagram ) inoh 8
STAT1 Gene expression of SOCS3 by STAT dimer ( JAK-STAT pathway and regulation pathway Diagram ) inoh 8
STAT1 Glucocorticoid receptor regulatory network pid 85
STAT1 GMCSF-mediated signaling events pid 38
STAT1 Growth hormone receptor signaling reactome 24
STAT1 IFN-gamma pathway pid 43
STAT1 IFN alpha signaling pathway((JAK1 TYK2 STAT1 STAT2) ( IFN alpha signaling(JAK1 TYK2 STAT1 STAT2 STAT3) ) inoh 20
STAT1 IFN alpha signaling pathway(JAK1 TYK2 STAT1 STAT3) ( IFN alpha signaling(JAK1 TYK2 STAT1 STAT2 STAT3) ) inoh 19
STAT1 IFN alpha signaling pathway(JAK1 TYK2 STAT1) ( IFN alpha signaling(JAK1 TYK2 STAT1 STAT2 STAT3) ) inoh 18
STAT1 IFN gamma signaling pathway(JAK1 JAK2 STAT1) ( IFN gamma signaling(JAK1 JAK2 STAT1) ) inoh 6
STAT1 IL-5 signaling pathway(JAK1 JAK2 STAT1 STAT5) ( IL-5 signaling(JAK1 JAK2 STAT1 STAT5) ) inoh 11
STAT1 IL-7 netpath 28
STAT1 IL12-mediated signaling events pid 62
STAT1 IL2-mediated signaling events pid 54
STAT1 IL2 netpath 81
STAT1 IL23-mediated signaling events pid 37
STAT1 IL27-mediated signaling events pid 26
STAT1 IL4 netpath 75
STAT1 IL5 netpath 59
STAT1 IL6-mediated signaling events pid 48
STAT1 IL6 netpath 85
STAT1 IL9 netpath 24
STAT1 Interferon-gamma signaling pathway panther 29
STAT1 Interferon alpha/beta signaling reactome 67
STAT1 Interferon gamma signaling reactome 88
STAT1 Interleukin-6 signaling reactome 11
STAT1 Interleukin signaling pathway panther 86
STAT1 ISG15 antiviral mechanism reactome 73
STAT1 JAK-STAT pathway and regulation pathway ( JAK-STAT pathway and regulation pathway Diagram ) inoh 97
STAT1 JAK/STAT signaling pathway panther 15
STAT1 KitReceptor netpath 104
STAT1 Leptin netpath 98
STAT1 Oxidative stress response panther 23
STAT1 PDGF signaling pathway panther 113
STAT1 PDGFR-beta signaling pathway pid 125
STAT1 Positive regulation of (Transcription of SOCS by STAT dimer) in JAK STAT pathway ( JAK-STAT pathway and regulation pathway Diagram ) inoh 178
STAT1 Prolactin netpath 105
STAT1 RANKL netpath 84
STAT1 Ras Pathway panther 69
STAT1 Regulation of IFNA signaling reactome 26
STAT1 Regulation of IFNG signaling reactome 14
STAT1 SHP2 signaling pid 60
STAT1 Signaling by cytosolic FGFR1 fusion mutants reactome 18
STAT1 Signaling by SCF-KIT reactome 37
STAT1 Signaling events mediated by Stem cell factor receptor (c-Kit) pid 53
STAT1 Signaling events mediated by TCPTP pid 40
STAT1 TCR netpath 261
STAT1 TNF receptor signaling pathway pid 46
STAT1 TNFalpha netpath 274
STAT1 TSH netpath 82
STAT1 TSLP netpath 24
STAT1 Chemokine signaling pathway kegg 187
STAT1 Toll-like receptor signaling pathway kegg 100
STAT1 Jak-STAT signaling pathway kegg 149
STAT1 Leishmaniasis kegg 71
STAT1 Toxoplasmosis kegg 131
STAT1 Hepatitis C kegg 134
STAT1 Pathways in cancer kegg 321
STAT1 Pancreatic cancer kegg 70
STAT1 Hs_Interferon_type_I_signaling_pathways_WP585_85198 wikipathways 35
STAT1 Hs_Cytokines_and_Inflammatory_Response_WP530_79331 wikipathways 21
STAT1 Hs_Leptin_signaling_pathway_WP2034_89856 wikipathways 37
STAT1 Hs_Interleukin-11_Signaling_Pathway_WP2332_79525 wikipathways 17
STAT1 Hs_Endochondral_Ossification_WP474_87977 wikipathways 43
STAT1 Hs_Integrated_Breast_Cancer_Pathway_WP1984_82941 wikipathways 122
STAT1 Hs_PDGF_Pathway_WP2526_82681 wikipathways 12
STAT1 Hs_Endoderm_Differentiation_WP2853_88152 wikipathways 62
STAT1 Hs_VEGFA-VEGFR2_Signaling_Pathway_WP3888_90000 wikipathways 153
STAT1 Hs_Integrated_Cancer_Pathway_WP1971_82939 wikipathways 33
STAT1 Hs_Oncostatin_M_Signaling_Pathway_WP2374_73668 wikipathways 44
STAT1 Hs_One_carbon_metabolism_and_related_pathways_WP3940_91096 wikipathways 10
STAT1 Hs_Kit_receptor_signaling_pathway_WP304_78799 wikipathways 46
STAT1 Hs_IL-5_Signaling_Pathway_WP127_78498 wikipathways 35
STAT1 Hs_IL-2_Signaling_Pathway_WP49_91243 wikipathways 33
STAT1 Hs_IL-6_signaling_pathway_WP364_89832 wikipathways 26
STAT1 Hs_Prolactin_Signaling_Pathway_WP2037_90015 wikipathways 52
STAT1 Hs_IL-4_Signaling_Pathway_WP395_89828 wikipathways 41
STAT1 Hs_Brain-Derived_Neurotrophic_Factor_(BDNF)_signaling_pathway_WP2380_89803 wikipathways 80
STAT1 Hs_EGF-EGFR_Signaling_Pathway_WP437_79266 wikipathways 107
STAT1 Hs_IL-9_Signaling_Pathway_WP22_79264 wikipathways 11
STAT1 Hs_Insulin_signalling_in_adipocytes_(diabetic_condition)_WP3635_86059 wikipathways 6
STAT1 Hs_Insulin_signalling_in_adipocytes_(normal_condition)_WP3634_86060 wikipathways 6

Enhancer associated network

The number on yellow line represents the distance between enhancer and target gene

Expression of target genes for the enhancer

Enhancer associated SNPs