I am trying to find if my gene of interest (ACVRL1) has a hypoxia response element in its human, rat, mouse promoters? Is there a way to do this online?
I major in Bioinformatics for plant and have no knowledge about animal or human. But in terms of motif search, I think publicly available databases relevant may do you favor. Such as Promoter Database (https://cb.utdallas.edu/cgi-bin/TRED/tred.cgi?process=home). Or, you can do it by yourself with pattern search against your promoter region with the known promoter motifs
This may sound like a simple question, but performing retrospective motif analysis is often complicated. First, while gene regulation by a certain signal (e.g. hypoxia) may be conserved across species, the location of the regulatory elements in the genome that mediate this response are often not conserved (that is, an HRE may exist in all three species of interest, but their location in the promoter will change). In general, conservation of motifs at any given site is low across species, and this negative result is not informative (it does NOT mean that the gene isn't regulated by hypoxia).
Second, you can always find a motif of interest, if you either increase your sequence search space enough by increasing the distance from the gene TSS, or by lowering your threshold for a motif match (allow more mismatches from the canonical sequence). So informatics tools will nearly always find some matches for your motif of interest, if you don't make the search too stringent. But these positive hits don't mean much, especially since it is universally known that the number of theoretical binding sites (motif occurrences) for transcription factors in the genome vastly exceed the number of true binding sites. Many sites are non-functional/non-accessible for transcription factors due to repressive effects of chromatin.
Third, many enhancers act at long-range distances, so focusing solely on gene-proximal sites tells an incomplete story. Long range interactions have been shown to be particularly important in gene regulation by hypoxia, see PMID 21447827. This paper should shed some light on ACVR1 in MCF7 cells.
The only way to really know if there is a bound HRE in all these species is to perform ChIP experiments for factors such as HIF1alpha. You can also look in a variety of databases for motif or TF binding sites, but none are comprehensive:
http://mpromdb.wistar.upenn.edu/
http://www.sabiosciences.com/chipqpcrsearch.php?app=TFBS
http://ecrbrowser.dcode.org
Have you tried to look at previously published microarray data from similar experiments?
Here is a generic video that attempts to explain how researchers are solving biological questions with previously published data.
I'd love to hear your comments about this.
Thanks,
Alain
https://vimeo.com/125323142
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