Regulatory features between INSIG1 and BLACE in human
-
Find the Location tab (Region in detail view) for the region between the genes INSIG1 and BLACE. Are there any predicted enhancers in this region?
-
Go to the Regulation tab for the enhancer ENSR00001133586. How many cell types is this enhancer active in? Are there any cell types where its activity is repressed?
-
Switch to the Location tab. Take a look at the histone modifications across this enhancer in neutro myelocyte cells, where this enhancer is active, compared to neutrophil (CB) cells, where it is poised. What differences can you observe?
-
Are there any verified transcription factor binding motifs in this enhancer? In what cells?
- Search for
human INSIG1
from the Ensembl homepage. Click on INSIG1 genomic coordinates 7:155297776-155310235:1 in the search results to open the Location tab directly. In the Region overview display, drag out a box to encompass the neighbouring BLACE gene. Scroll down to the Region in detail display. Have a look at the Regulatory Build track. You can find a legend of this track underneath the display.There are 5 yellow enhancers in the region between the genes INSIG1 and BLACE.
- There are several ways to search for the enhancer. You can click the different enhancer features in the Regulatory Build track to find ENSR00001133586, or you can search Ensembl for the ID ENSR00001133586 and navigate to the Regulation tab. Under the Activity display, you can find the activity of the regulatory feature across different cell types.
ENSR00001133586 is active in neutro myelocyte cells only. It is repressed in 34 cell types.
- Click on the Location tab. Choose cells by clicking on the Configure this page button on the left-hand panel or Add/remove tracks button above the Region in detail display. In the pop-up window, click on Features by Cell/Tissue in the left-hand menu. Select neutro myelocyte in which this enhancer is active and neutrophil (CB) in which it is poised. Add experiment tracks by clicking on Experiments tab and Select all under Histone. Click Configure track display, then View tracks to load the page.
Both cell types have H3K27me3, H3K4me1 and H3K9me3 histone modifications at this locus, while neutro myelocyte cells also have H3K27ac and H3K36me3 modifications, and neutrophils (CB) have H3K4me3 modifications. The different clusters of peaks indicate different epigenetic profiles, which might explain the difference in the enhancer activity between these two cell types.
- Stay in the Location tab. Click on the Configure this page button on the left-hand panel or Add/remove tracks button above the Region in detail display. In the pop-up window in the left-hand menu, go to the Regulation section and click on Other regulatory regions. Enable the Motif features track to visualise any transcription factor (TF) binding motifs. Close the pop-up window. Find the Motif features track. There are two black markers indicating verified TF motifs. Click on them to tell which motifs and which cells.
The two motifs are both verified in K562 cells and bind a number of different TFs. The ENSM00523362328 motif binds ELF1, ELF2, ELK1, FLI1, ERG, ETS1, ETV6, FOXO1::ELK3, FOXO1::ETV1, ETV1, ETV2, ERF, ELK3, ETV3, GABPA, ETS2, ELK4, FEV, ETV5 and ETV4. ENSM00523900117 binds ETV7, ETS1 and ELK1::SPDEF.