About Enhancer

Enhancer ID: E_02_0768
Species: human
Position : chr14:56245000-56285000
Biosample name:
Experiment class : Low+High throughput
Enhancer type: Enhancer
Disease: --
Pubmed ID:  29348663
Enhancer experiment: ChIP-seq,qPCR,Hi-C
Enhancer experiment description: To test this possibility, we first attempted to identify the promoter/enhancer region of LEENE. In evaluating the genomic region surrounding LEENE, i.e., 20?kb up- and down-stream of the transcription start site (TSS) on chr14: 56,245,00056,285,000, we observed the enrichments of H3K27ac and H3K4me1 in the HUVEC chromatin immunoprecipitation (ChIP)-seq data available in the ENCODE Database, indicating an enhancer state of this DNA region.We did find that PS led to significant increase in the H3K27ac in the LEENE region as measured by ChIP-qPCR, indicating the activation of LEENE as an enhancer in ECs subjected to PS vs.

About Target gene

Target gene : LINC00520(C14orf34),LINC00520(C14orf34),LINC00520(C14orf34)
Strong evidence: --
Less strong evidence: ChIP-qPCR,qPCR,Hi-C
Target gene experiment description: As shown in Fig. 1f, quantitative PCR (qPCR) with LEENE RNA-specific primers also revealed the significantly higher level of LEENE in ECs subjected to PS than to OS. To confirm the flow regulation of LEENE in ECs and explore its relevance to endothelial function, we tested whether LEENE is differentially regulated by tumor necrosis factor alpha (TNF?), which exerts pro-inflammatory effects similar to OS, and atorvastatin (ATV), which confers endothelial protective effects similar to PS. Resembling the opposite effects of OS and PS, TNF? decreased, while ATV increased the level of LEENE.These findings are in line with the differential levels of KLF2/KLF4-eNOS signaling.;As shown in Fig. 1f, quantitative PCR (qPCR) with LEENE RNA-specific primers also revealed the significantly higher level of LEENE in ECs subjected to PS than to OS. To confirm the flow regulation of LEENE in ECs and explore its relevance to endothelial function, we tested whether LEENE is differentially regulated by tumor necrosis factor alpha (TNF?), which exerts pro-inflammatory effects similar to OS, and atorvastatin (ATV), which confers endothelial protective effects similar to PS. Resembling the opposite effects of OS and PS, TNF? decreased, while ATV increased the level of LEENE.These findings are in line with the differential levels of KLF2/KLF4-eNOS signaling.;As shown in Fig. 1f, quantitative PCR (qPCR) with LEENE RNA-specific primers also revealed the significantly higher level of LEENE in ECs subjected to PS than to OS. To confirm the flow regulation of LEENE in ECs and explore its relevance to endothelial function, we tested whether LEENE is differentially regulated by tumor necrosis factor alpha (TNF?), which exerts pro-inflammatory effects similar to OS, and atorvastatin (ATV), which confers endothelial protective effects similar to PS. Resembling the opposite effects of OS and PS, TNF? decreased, while ATV increased the level of LEENE.These findings are in line with the differential levels of KLF2/KLF4-eNOS signaling.

About TF

TF name : KLF2(LKLF)KLF4(EZF,GKLF)KLF2(LKLF)KLF4(EZF,GKLF)KLF2(LKLF)KLF4(EZF,GKLF)
TF experiment: ChIP-qPCR
TF experiment description: To confirm the association of such TFs on the promoter of LEENE, we performed ChIP-qPCR, which detected a robust binding between KLF4 and multiple regions within the promoter region of LEENE (marked by H3K4me3 peaks, Fig. 2a); these interactions were significantly increased by Ad-KLF4, which mimics the effect of PS and ATV.;To confirm the association of such TFs on the promoter of LEENE, we performed ChIP-qPCR, which detected a robust binding between KLF4 and multiple regions within the promoter region of LEENE (marked by H3K4me3 peaks, Fig. 2a); these interactions were significantly increased by Ad-KLF4, which mimics the effect of PS and ATV.;To confirm the association of such TFs on the promoter of LEENE, we performed ChIP-qPCR, which detected a robust binding between KLF4 and multiple regions within the promoter region of LEENE (marked by H3K4me3 peaks, Fig. 2a); these interactions were significantly increased by Ad-KLF4, which mimics the effect of PS and ATV.

About Function

Enhancer function : LEENE-associated Enhancer plays a role in positive regulation of eNOS transcription
Enhancer function experiment: CRISPR/Cas9
Enhancer function
experiment description:
As a result of the Enhancer ablation, the transcription of LEENE and eNOS was significantly suppressed, in both DMSO (a control vehicle) and ATV-treated ECs

About SNP

SNP ID: --

Upstream Pathway Annotation of TF

GeneName Pathway Name Source Gene Number
KLF2 Hs_White_fat_cell_differentiation_WP3946_90940 wikipathways 30
KLF4 Regulation of nuclear beta catenin signaling and target gene transcription pid 80
KLF4 Synthesis, secretion, and deacylation of Ghrelin reactome 17
KLF4 Transcriptional regulation of pluripotent stem cells reactome 28
KLF4 Transcriptional regulation of white adipocyte differentiation reactome 79
KLF4 Hs_Role_of_Osx_and_miRNAs_in_tooth_development_WP3971_91525 wikipathways 9
KLF4 Hs_White_fat_cell_differentiation_WP3946_90940 wikipathways 30
KLF4 Hs_Mesodermal_Commitment_Pathway_WP2857_87780 wikipathways 47
KLF2 Hs_White_fat_cell_differentiation_WP3946_90940 wikipathways 30
KLF4 Regulation of nuclear beta catenin signaling and target gene transcription pid 80
KLF4 Synthesis, secretion, and deacylation of Ghrelin reactome 17
KLF4 Transcriptional regulation of pluripotent stem cells reactome 28
KLF4 Transcriptional regulation of white adipocyte differentiation reactome 79
KLF4 Hs_Role_of_Osx_and_miRNAs_in_tooth_development_WP3971_91525 wikipathways 9
KLF4 Hs_White_fat_cell_differentiation_WP3946_90940 wikipathways 30
KLF4 Hs_Mesodermal_Commitment_Pathway_WP2857_87780 wikipathways 47
KLF2 Hs_White_fat_cell_differentiation_WP3946_90940 wikipathways 30
KLF4 Regulation of nuclear beta catenin signaling and target gene transcription pid 80
KLF4 Synthesis, secretion, and deacylation of Ghrelin reactome 17
KLF4 Transcriptional regulation of pluripotent stem cells reactome 28
KLF4 Transcriptional regulation of white adipocyte differentiation reactome 79
KLF4 Hs_Role_of_Osx_and_miRNAs_in_tooth_development_WP3971_91525 wikipathways 9
KLF4 Hs_White_fat_cell_differentiation_WP3946_90940 wikipathways 30
KLF4 Hs_Mesodermal_Commitment_Pathway_WP2857_87780 wikipathways 47

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