About Enhancer

Enhancer ID: E_01_0731
Species: human
Position : chr3:189628438-189630438
Biosample name:
Experiment class : High+Lowthroughput
Enhancer type: Enhancer
Disease: Squamous cell carcinomas (sccs)
Pubmed ID:  30190462
Enhancer experiment: qRT-PCR,weston blot,RNA-seq,plasmid transfection,ChIP-seq
Enhancer experiment description: Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways.

About Target gene

Target gene : --
Strong evidence: qRT-PCR,qPCR,ChIP,3C
Less strong evidence: RNA-Seq
Target gene experiment description: Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. ;Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. ;Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways.

About TF

TF name : TP63(AIS,B(p51A),B(p51B),EEC3,KET,LMS,NBP,OFC8,RHS,SHFM4,TP53CP,TP53L,TP73L,p40,p51,p53CP,p63,p73H,p73L)SOX2(ANOP3,MCOPS3)EGFR
TF experiment: qRT-PCR,weston blot,RNA-seq,plasmid transfection,ChIP-seq
TF experiment description: Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. ;Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. ;Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways.

About Function

Enhancer function : Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways.
Enhancer function experiment: Immunohistochemical staining
Enhancer function
experiment description:		 Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways.

About SNP

SNP ID: --

Upstream Pathway Annotation of TF

GeneName Pathway Name Source Gene Number
TP63 Activation of PUMA and translocation to mitochondria reactome 8
TP63 Direct p53 effectors pid 141
TP63 Huntington disease panther 113
TP63 p53 pathway by glucose deprivation panther 21
TP63 p53 pathway panther 39
TP63 P53 pathway feedback loops 1 panther 6
TP63 p53 pathway feedback loops 2 panther 42
TP63 p73 transcription factor network pid 80
TP63 Regulation of TP53 Activity through Association with Co-factors reactome 14
TP63 TP53 Regulates Metabolic Genes reactome 85
TP63 TP53 Regulates Transcription of Caspase Activators and Caspases reactome 12
TP63 TP53 Regulates Transcription of Death Receptors and Ligands reactome 12
TP63 TP53 Regulates Transcription of Genes Involved in Cytochrome C Release reactome 19
TP63 TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain reactome 14
TP63 Validated transcriptional targets of deltaNp63 isoforms pid 47
TP63 Validated transcriptional targets of TAp63 isoforms pid 54
TP63 Hs_Focal_Adhesion_WP306_80308 wikipathways 26
TP63 Hs_TGF-beta_Receptor_Signaling_WP560_90187 wikipathways 28
TP63 Hs_Urea_cycle_and_metabolism_of_amino_groups_WP497_72142 wikipathways 8
TP63 Hs_Hypothetical_Craniofacial_Development_Pathway_WP3655_88473 wikipathways 5
SOX2 Deactivation of the beta-catenin transactivating complex reactome 42
SOX2 POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation reactome 13
SOX2 POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation reactome 10
SOX2 Transcriptional regulation of pluripotent stem cells reactome 28
SOX2 Hs_Endoderm_Differentiation_WP2853_88152 wikipathways 62
SOX2 Hs_Dopaminergic_Neurogenesis_WP2855_87239 wikipathways 19
SOX2 Hs_Wnt_Signaling_Pathway_and_Pluripotency_WP399_90291 wikipathways 12
SOX2 Hs_Mesodermal_Commitment_Pathway_WP2857_87780 wikipathways 47
SOX2 Hs_Ectoderm_Differentiation_WP2858_89329 wikipathways 56
EGFR a6b1 and a6b4 Integrin signaling pid 46
EGFR AKT(PKB)-Bad signaling ( EPO signaling pathway(JAK2 STAT1 STAT3 STAT5) ) inoh 173
EGFR AKT(PKB)-Bad signaling ( IL-7 signaling(JAK1 JAK3 STAT5) ) inoh 173
EGFR Alpha6Beta4Integrin netpath 74
EGFR AndrogenReceptor netpath 167
EGFR Arf6 signaling events pid 36
EGFR Cadherin signaling pathway panther 147
EGFR Constitutive Signaling by Aberrant PI3K in Cancer reactome 61
EGFR Constitutive Signaling by EGFRvIII reactome 15
EGFR Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants reactome 19
EGFR Direct p53 effectors pid 141
EGFR Drosophila Toll-like receptor signaling ( Drosophila Toll-like receptor signaling ) inoh 236
EGFR E-cadherin signaling in keratinocytes pid 21
EGFR EGF receptor signaling pathway panther 109
EGFR EGF signaling pathway ( EGF signaling pathway Diagram ) inoh 13
EGFR EGFR-dependent Endothelin signaling events pid 9
EGFR EGFR downregulation reactome 27
EGFR EGFR Transactivation by Gastrin reactome 9
EGFR EGFR1 netpath 475
EGFR ErbB receptor signaling network pid 15
EGFR ErbB1 downstream signaling pid 105
EGFR ERBB2 Activates PTK6 Signaling reactome 13
EGFR ERBB2 Regulates Cell Motility reactome 15
EGFR FAS signaling pathway panther 37
EGFR FSH netpath 44
EGFR GAB1 signalosome reactome 11
EGFR GRB2 events in EGFR signaling reactome 7
EGFR GRB2 events in ERBB2 signaling reactome 16
EGFR Internalization of ErbB1 pid 38
EGFR Leptin netpath 98
EGFR LPA receptor mediated events pid 65
EGFR PI3K events in ERBB2 signaling reactome 16
EGFR PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling reactome 83
EGFR PIP3 activates AKT signaling reactome 81
EGFR Positive regulation of (Transcription of SOCS by STAT dimer) in JAK STAT pathway ( JAK-STAT pathway and regulation pathway Diagram ) inoh 178
EGFR Posttranslational regulation of adherens junction stability and dissassembly pid 50
EGFR Prolactin netpath 105
EGFR PTK6 promotes HIF1A stabilization reactome 6
EGFR RAF/MAP kinase cascade reactome 116
EGFR RANKL netpath 84
EGFR Regulation of Telomerase pid 70
EGFR SHC1 events in EGFR signaling reactome 8
EGFR SHC1 events in ERBB2 signaling reactome 18
EGFR SHP2 signaling pid 60
EGFR Signal transduction by L1 reactome 21
EGFR Signaling by EGFR reactome 7
EGFR Signaling by ERBB2 reactome 25
EGFR Signaling by ERBB4 reactome 11
EGFR Signaling events mediated by PTP1B pid 53
EGFR Signaling events mediated by TCPTP pid 40
EGFR Stabilization and expansion of the E-cadherin adherens junction pid 43
EGFR Syndecan-3-mediated signaling events pid 23
EGFR Thromboxane A2 receptor signaling pid 56
EGFR TNFalpha netpath 274
EGFR Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling pid 42
EGFR VEGF signaling pathway ( VEGF signaling pathway ) inoh 183
EGFR MAPK signaling pathway kegg 264
EGFR ErbB signaling pathway kegg 83
EGFR MAPK signaling pathway - fly kegg 16
EGFR Calcium signaling pathway kegg 173
EGFR Cytokine-cytokine receptor interaction kegg 213
EGFR Endocytosis kegg 201
EGFR Dorso-ventral axis formation kegg 25
EGFR Focal adhesion kegg 197
EGFR Adherens junction kegg 70
EGFR Gap junction kegg 87
EGFR Regulation of actin cytoskeleton kegg 210
EGFR GnRH signaling pathway kegg 98
EGFR Epithelial cell signaling in Helicobacter pylori infection kegg 67
EGFR Hepatitis C kegg 134
EGFR Pathways in cancer kegg 321
EGFR Pancreatic cancer kegg 70
EGFR Endometrial cancer kegg 52
EGFR Glioma kegg 65
EGFR Prostate cancer kegg 85
EGFR Melanoma kegg 69
EGFR Bladder cancer kegg 38
EGFR Non-small cell lung cancer kegg 54
EGFR Hs_ErbB_Signaling_Pathway_WP673_91869 wikipathways 37
EGFR Hs_Corticotropin-releasing_hormone_signaling_pathway_WP2355_90017 wikipathways 41
EGFR Hs_Association_Between_Physico-Chemical_Features_and_Toxicity_Associated_Pathways_WP3680_90113 wikipathways 31
EGFR Hs_MAPK_Signaling_Pathway_WP382_79951 wikipathways 58
EGFR Hs_Gastric_Cancer_Network_2_WP2363_87523 wikipathways 28
EGFR Hs_Integrated_Breast_Cancer_Pathway_WP1984_82941 wikipathways 122
EGFR Hs_Rac1-Pak1-p38-MMP-2_pathway_WP3303_87628 wikipathways 32
EGFR Hs_BMP_Signaling_Pathway_in_Eyelid_Development_WP3927_90735 wikipathways 11
EGFR Hs_Bladder_Cancer_WP2828_89143 wikipathways 17
EGFR Hs_Aryl_Hydrocarbon_Receptor_Pathway_WP2873_88902 wikipathways 5
EGFR Hs_ERK_Pathway_in_Huntington's_Disease_WP3853_89748 wikipathways 10
EGFR Hs_TGF-beta_Signaling_Pathway_WP366_90028 wikipathways 67
EGFR Hs_AGE-RAGE_pathway_WP2324_89798 wikipathways 27
EGFR Hs_Androgen_receptor_signaling_pathway_WP138_79958 wikipathways 27
EGFR Hs_EGF-EGFR_Signaling_Pathway_WP437_79266 wikipathways 107

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