About Enhancer
| Enhancer ID: | E_02_0803 |
| Species: | human |
| Position : | chr5:9034150-9036900   |
| Biosample name: | |
| Experiment class : | Low+High throughput |
| Enhancer type: | Super-Enhancer |
| Disease: | -- |
| Pubmed ID: | 28335007 |
| Enhancer experiment: | ChIP-seq |
| Enhancer experiment description: | On the other hand, the enhancer regions associated with lncRNAs tended to have much higher intensities of H3K27ac marks than the enhancers not associated with lncRNAs (KS test, P-value < 2.2 10?16) (Figure ?(Figure2E).2E). The enhancers associated with circadian lncRNAs have even higher levels of H3K27ac marks than those associated with lncRNAs (KS test, P-value = 0.0017). Taken together, there is a strong association between circadian lncRNAs and super-enhancers. |
About Target gene
| Target gene : | Gm40264(lnc-Crot),Gm40264(lnc-Crot) |
| Strong evidence: | 4C |
| Less strong evidence: | qPCR,RNA-seq,ChIP-seq |
| Target gene experiment description: | The enhancers defined from mouse liver GRO-seq and 5? CAGE technology were consistent with H3K27ac marks of enhancer at this lnc-Crot region (Supplementary Figure S3C). Using RACE assay, we obtained the full-length sequence of lnc-Crot (Figure ?(Figure4B).4B). Both BMAL1 and REV-ERB? binding sites were found on the promoter and gene body of lnc-Crot (Figure ?(Figure4B)4B) but not on the promoters of nearby circadian genes including Crot, Tmem243 and Dmtf1 (Supplementary Figure S3D).By qPCR, we showed that Crot and lnc-Crot were co-expressed (r = 0.8) across adult mouse tissues with elevated expression in liver and kidney (Supplementary Figure S3F).4C signals from three biological replicates at each circadian time were highly reproducible judging from their cross-sample correlations between 0.89 and 0.95. About 44% of 4C signals fell within chromosome 5 where lnc-Crot is situated and the signal profile around lnc-Crot region was displayed in Supplementary Figure S5A. ;The enhancers defined from mouse liver GRO-seq and 5? CAGE technology were consistent with H3K27ac marks of enhancer at this lnc-Crot region (Supplementary Figure S3C). Using RACE assay, we obtained the full-length sequence of lnc-Crot (Figure ?(Figure4B).4B). Both BMAL1 and REV-ERB? binding sites were found on the promoter and gene body of lnc-Crot (Figure ?(Figure4B)4B) but not on the promoters of nearby circadian genes including Crot, Tmem243 and Dmtf1 (Supplementary Figure S3D).By qPCR, we showed that Crot and lnc-Crot were co-expressed (r = 0.8) across adult mouse tissues with elevated expression in liver and kidney (Supplementary Figure S3F).4C signals from three biological replicates at each circadian time were highly reproducible judging from their cross-sample correlations between 0.89 and 0.95. About 44% of 4C signals fell within chromosome 5 where lnc-Crot is situated and the signal profile around lnc-Crot region was displayed in Supplementary Figure S5A. |
About TF
| TF name : | Arntl(BMAL1,BMAL1c,JAP3,MOP3,PASD3,TIC,bHLHe5)Nr1d2(RVR,Rev-erb)Arntl(BMAL1,BMAL1c,JAP3,MOP3,PASD3,TIC,bHLHe5)Nr1d2(RVR,Rev-erb) |
| TF experiment: | ChIP-seq,RNA-seq,Knockout mice |
| TF experiment description: | We defined BMAL1 and REV-ERB binding sites from two sets of BMAL1 ChIP-seq studies and two sets of REV-ERB ChIP-seq data in mouse liver respectively, resulting in 8001 BMAL1and 17545REV-ERB binding sites.Atotal of 259 (43%) circadian lncRNA clusters contain either BMAL1 or REV-ERB binding sites.For each lncRNA cluster, we quantified its expression in the BMAL1 knockout and WT mouse livers at CT0 and CT12 using our RNA-seq data.This suggested that circadian lncRNAs were regulated by these two master circadian TFs in the similar way as circadian protein coding genes.Circadian expression of lnc-Crot was disrupted when BMAL1 or REV-ERB? was knocked out, resulting in its downregulation at CT0 in BMAL1 knockout mice and upregulation at CT12 in REV-ERB? knockout mice (Figure ?(Figure4B,4B, Supplementary Figure S3E). This demonstrated that lnc-Crot was directly regulated by BMAL1 and REV-ERB?.;We defined BMAL1 and REV-ERB binding sites from two sets of BMAL1 ChIP-seq studies and two sets of REV-ERB ChIP-seq data in mouse liver respectively, resulting in 8001 BMAL1and 17545REV-ERB binding sites.Atotal of 259 (43%) circadian lncRNA clusters contain either BMAL1 or REV-ERB binding sites.For each lncRNA cluster, we quantified its expression in the BMAL1 knockout and WT mouse livers at CT0 and CT12 using our RNA-seq data.This suggested that circadian lncRNAs were regulated by these two master circadian TFs in the similar way as circadian protein coding genes.Circadian expression of lnc-Crot was disrupted when BMAL1 or REV-ERB? was knocked out, resulting in its downregulation at CT0 in BMAL1 knockout mice and upregulation at CT12 in REV-ERB? knockout mice (Figure ?(Figure4B,4B, Supplementary Figure S3E). This demonstrated that lnc-Crot was directly regulated by BMAL1 and REV-ERB?. |
About Function
| Enhancer function : | Enhancer-associated circadian lncRNAs mark the genomic loci modulating long-range circadian gene regulation and shed new lights on the evolutionary origin of lncRNAs. |
| Enhancer function experiment: | qPCR,CRISPR/Cas9 |
| Enhancer function experiment description: |
Our result points to a model that the lnc-Crot locus and nearby genes first form a scaffold upon which histone modifications and TF bindings then take place to confer tissue- and time-dependent expression (Figure ?(Figure5G).5G). The circadian lncRNAs that we examined may be a result of circadian transcription at the enhancer regions while the lncRNAs themselves do not influence the circadian gene regulation. |
About SNP
| SNP ID: | -- |
Upstream Pathway Annotation of TF
Enhancer associated network
The number on yellow line represents the distance between enhancer and
target gene