About Enhancer

Enhancer ID: E_02_0981
Species: mouse
Position : chr13:53463266-53463541
Biosample name:
Experiment class : Low throughput
Enhancer type: Enhancer
Disease: --
Pubmed ID:  20878775
Enhancer experiment: PCR,Luciferase Reporter Assay
Enhancer experiment description: The murine Dlx5 promoter from -1036 to +30 was obtained by polymerase chain reaction (PCR) and cloned in the pGL2basic vector. Murine Msx2 and Runx2 enhancers (from -3340 to -3615 for Msx2 and from -1170 to -1388 for Runx2) also were obtained by PCR and subcloned in the minimal promoter of c-fos promoter.

About Target gene

Target gene : Msx2(BB122635,Hox-8,Hox8,Hox8.1),Msx2(BB122635,Hox-8,Hox8,Hox8.1)
Strong evidence: --
Less strong evidence: Luciferase Reporter Assay
Target gene experiment description: The Msx2 gene shows a conserved region 3.5 kb upstream of the transcriptional start site, which also includes a combination of a TCF/LEF1 box and both GC-rich and CAGA SBEs. This region has been shown to be necessary and sufficient to confer BMP responsiveness in vitro and in vivo.Finally, a similar enhancer is located 1 kb upstream of the P1 osteoblast-specific promoter of the Runx2 gene (Supplemental Fig. S3). To test whether these regions have the ability to render responsiveness to Wnt3a and/or BMP-2, we generated the corresponding luciferase constructs and assayed them in C2C12 cells. ;The Msx2 gene shows a conserved region 3.5 kb upstream of the transcriptional start site, which also includes a combination of a TCF/LEF1 box and both GC-rich and CAGA SBEs. This region has been shown to be necessary and sufficient to confer BMP responsiveness in vitro and in vivo.Finally, a similar enhancer is located 1 kb upstream of the P1 osteoblast-specific promoter of the Runx2 gene (Supplemental Fig. S3). To test whether these regions have the ability to render responsiveness to Wnt3a and/or BMP-2, we generated the corresponding luciferase constructs and assayed them in C2C12 cells.

About TF

TF name : Msx2(BB122635,Hox-8,Hox8,Hox8.1)Dlx3(AV237891,Dlx-3)Dlx5(AI385752)Atf4Runx2(AML3,Cbf,Cbfa-1,Cbfa1,LS3,Osf2,PEBP2aA,Pebp2a1,Pebpa2a)Sp7(6430578P22Rik,C22,Osx)Msx2(BB122635,Hox-8,Hox8,Hox8.1)Dlx3(AV237891,Dlx-3)Dlx5(AI385752)Atf4Runx2(AML3,Cbf,Cbfa-1,Cbfa1,LS3,Osf2,PEBP2aA,Pebp2a1,Pebpa2a)Sp7(6430578P22Rik,C22,Osx)
TF experiment: qRT-PCR,Luciferase Reporter Assay,ChIP
TF experiment description: To confirm that cooperative transcriptional interactions between canonical Wnt signaling and the Smad pathway on osteogenic genes occur in vivo, ChIP assays were performed in C2C12 cells.As shown in Fig.7D,TCF4,b-catenin,and Smad1 and Smad4 interacted with the responsive regions of Dlx5, Msx2, and Runx2 genes in vivo.;To confirm that cooperative transcriptional interactions between canonical Wnt signaling and the Smad pathway on osteogenic genes occur in vivo, ChIP assays were performed in C2C12 cells.As shown in Fig.7D,TCF4,b-catenin,and Smad1 and Smad4 interacted with the responsive regions of Dlx5, Msx2, and Runx2 genes in vivo.

About Function

Enhancer function : --
Enhancer function experiment: --
Enhancer function
experiment description:
--

About SNP

SNP ID: --

Upstream Pathway Annotation of TF

GeneName Pathway Name Source Gene Number
Msx2 Hs_Neural_Crest_Differentiation_WP2064_79263 wikipathways 40
Dlx5 Validated transcriptional targets of deltaNp63 isoforms pid 47
Dlx5 Hs_MECP2_and_Associated_Rett_Syndrome_WP3584_91190 wikipathways 12
Dlx5 Hs_Neural_Crest_Differentiation_WP2064_79263 wikipathways 40
Atf4 Apoptosis signaling pathway panther 104
Atf4 ATF4 activates genes reactome 25
Atf4 ATF6-alpha activates chaperone genes reactome 10
Atf4 Validated transcriptional targets of AP1 family members Fra1 and Fra2 pid 37
Atf4 MAPK signaling pathway kegg 264
Atf4 Protein processing in endoplasmic reticulum kegg 166
Atf4 Long-term potentiation kegg 67
Atf4 Neurotrophin signaling pathway kegg 126
Atf4 GnRH signaling pathway kegg 98
Atf4 Prostate cancer kegg 85
Atf4 Hs_VEGFA-VEGFR2_Signaling_Pathway_WP3888_90000 wikipathways 153
Atf4 Hs_White_fat_cell_differentiation_WP3946_90940 wikipathways 30
Atf4 Hs_One_Carbon_Metabolism_WP241_89671 wikipathways 14
Runx2 AndrogenReceptor netpath 167
Runx2 FGF signaling pathway pid 55
Runx2 Leptin netpath 98
Runx2 Notch-mediated HES/HEY network pid 48
Runx2 Regulation of nuclear SMAD2/3 signaling pid 82
Runx2 Regulation of retinoblastoma protein pid 67
Runx2 TGF_beta_Receptor netpath 220
Runx2 YAP1- and WWTR1 (TAZ)-stimulated gene expression reactome 29
Runx2 Hs_MAPK_Signaling_Pathway_WP382_79951 wikipathways 58
Runx2 Hs_Endochondral_Ossification_WP474_87977 wikipathways 43
Runx2 Hs_Role_of_Osx_and_miRNAs_in_tooth_development_WP3971_91525 wikipathways 9
Runx2 Hs_Bone_Morphogenic_Protein_(BMP)_Signalling_and_Regulation_WP1425_86082 wikipathways 6
Runx2 Hs_Focal_Adhesion-PI3K-Akt-mTOR-signaling_pathway_WP3932_91101 wikipathways 8
Sp7 Hs_Role_of_Osx_and_miRNAs_in_tooth_development_WP3971_91525 wikipathways 9
Msx2 Hs_Neural_Crest_Differentiation_WP2064_79263 wikipathways 40
Dlx5 Validated transcriptional targets of deltaNp63 isoforms pid 47
Dlx5 Hs_MECP2_and_Associated_Rett_Syndrome_WP3584_91190 wikipathways 12
Dlx5 Hs_Neural_Crest_Differentiation_WP2064_79263 wikipathways 40
Atf4 Apoptosis signaling pathway panther 104
Atf4 ATF4 activates genes reactome 25
Atf4 ATF6-alpha activates chaperone genes reactome 10
Atf4 Validated transcriptional targets of AP1 family members Fra1 and Fra2 pid 37
Atf4 MAPK signaling pathway kegg 264
Atf4 Protein processing in endoplasmic reticulum kegg 166
Atf4 Long-term potentiation kegg 67
Atf4 Neurotrophin signaling pathway kegg 126
Atf4 GnRH signaling pathway kegg 98
Atf4 Prostate cancer kegg 85
Atf4 Hs_VEGFA-VEGFR2_Signaling_Pathway_WP3888_90000 wikipathways 153
Atf4 Hs_White_fat_cell_differentiation_WP3946_90940 wikipathways 30
Atf4 Hs_One_Carbon_Metabolism_WP241_89671 wikipathways 14
Runx2 AndrogenReceptor netpath 167
Runx2 FGF signaling pathway pid 55
Runx2 Leptin netpath 98
Runx2 Notch-mediated HES/HEY network pid 48
Runx2 Regulation of nuclear SMAD2/3 signaling pid 82
Runx2 Regulation of retinoblastoma protein pid 67
Runx2 TGF_beta_Receptor netpath 220
Runx2 YAP1- and WWTR1 (TAZ)-stimulated gene expression reactome 29
Runx2 Hs_MAPK_Signaling_Pathway_WP382_79951 wikipathways 58
Runx2 Hs_Endochondral_Ossification_WP474_87977 wikipathways 43
Runx2 Hs_Role_of_Osx_and_miRNAs_in_tooth_development_WP3971_91525 wikipathways 9
Runx2 Hs_Bone_Morphogenic_Protein_(BMP)_Signalling_and_Regulation_WP1425_86082 wikipathways 6
Runx2 Hs_Focal_Adhesion-PI3K-Akt-mTOR-signaling_pathway_WP3932_91101 wikipathways 8
Sp7 Hs_Role_of_Osx_and_miRNAs_in_tooth_development_WP3971_91525 wikipathways 9

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