Estrogen receptor (ER) is an important transcription factor, which is up-regulated in 70% of all breast cancers

Estrogen receptor is an important transcription factor, which is up-regulated in 70% of all breast cancers. Using the known ER motif to scan the genome yields many thousands of matches, although not all of them are functional. Given the following four matches to the motif, use a comparative genomics approach to judge which one is most likely functional.

Response: Please see the attached Word document for a complete answer with graphic output from the UCSC Genome Browser.

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If we go to the UCSC Genome Browser at http://genome.ucsc.edu/cgi-bin/hgGateway, we can plug these coordinates into the genome, extract the data, and analyze it.

We'll do each one in turn. First, we start with (a). Here's a graphic illustration of the output for the (a) region. If we look at the conservation section, we see that there is some similarity, but only with dog and elephant, and even then, only at the beginning of the sequence. You can see this effect if you look at the dark blue line immediately above the word "Gaps". This is showing how promising the conservation truly is. It's thicker on the left side and fades out toward the right. This doesn't look too promising if it's really a true ER motif in a functional gene.

[graphic]

Now, let's do (b). What do we see here? We see that there is really no match at all. Look at all of the mismatches in the conservation alignment below. And notice that there is no dark blue line showing any conservation at all!

[graphic]

Now, we go to (c) region. This is the one. The conservation is practically perfect among the species listed. Look at how it is almost identical among human, mouse, rat, rabbit, dog, armadillo, elephant, etc. Definitely, this is the one! See the big thick dark blue bar? Wow! It couldn't be plainer than the nose on my face!

[graphic]

In fact, if you click on the conservation portion of the graphic output (in the original web browser, not in this Word document), you will see the alignment:

Alignment block 1 of 1 in window, 15299684 - 15299702, 19 bps
B D Human gcgggttagtgtgaccttg
B D Mouse gcgggttagagtgaccttg
B D Rat gcgggttagtgtgaccttg
Rabbit gcgggttagtgtgaccttg
B D Dog gcgggttagtgtgaccttg
Armadillo gcgggttagtgtgaccttg
Elephant gcgggttagtgtgaccttg
B D Opossum ===================
B D Chicken gcgggttagcgtgaccttg
B D X. tropicalis gcgggttgggatgaccttg

It looks pretty good, doesn't it?

However, just to be sure, let's check (d). There's no conservation here at all.

[graphic]

Therefore, we conclude that sequence (c) is the likely candidate for a true ER motif in a true human gene. Pretty cool, eh?

PFA