Gene regulation: Human INSIG1 and BLACE
(a) Find the Location tab (Region in detail page) for the region between the genes INSIG1 and BLACE. Are there any predicted enhancers in this region?
(b) 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?
(c) Go to the Details by cell type page. 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?
(d) Go back to the Summary page. Are there any verified transcription factor binding motifs in this enhancer? In what cells?
(a) Search for human INSIG1 from the home page. Click on INSIG1 genomic coordinates 7:155297776-155310235:1 in the search results to open the Location tab.
In the region overview, drag out a box to encompass the neighbouring BLACE gene. Have a look at the Regulatory Build track.
There is one yellow enhancer in the region between these genes.
(b) Click on the enhancer to get a pop-up with its ID and other information. Click on the ID ENSR00001133586 to open the Regulation tab.
Scroll down to see the summary of regulatory activity across different cell types.
ENSR00001133586 is active in neutro myelocyte cells. It is repressed in 34 cell types.
(c) Click on Details by cell type at the top of the page or in the left-hand menu.
Choose cells by clicking on Configure Cell/Tissue blue button, then selecting 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 modifications at this locus, while neutro myelocyte cells also have H3K27ac and H3K36me3 modifications. Different clusters of peaks indicate different epigenetic profiles, which might explain the difference in the enhancer activity between these two cell types.
(d) Go back to the Summary view. In 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. One binds ELF1, ELF2, ELK1, FLI1, ERG, ETS1, ETV6, FOXO1::ELK3, FOXO1::ETV1, ETV1, ETV2, ERF, ELK3, ETV3, GABPA, ETS2, ELK4, FEV, ETV5 and ETV4. The other binds ETV7, ETS1 and ELK1::SPDEF.