Functional relationships between genes that are contiguous in the genome - (Apr/04/2012 )
I started a thread about this subject about one year ago but I can't find it.
I am studying a gene whose function is not described (let's call it gene "Y"). The protein possesses a domain that is found in some transcription factors of the zinc cluster family although no DNA binding domain is found by bioinformatics. In oppostion to the wild type, the knockout mutant for this protein is unable to induce some genes (when cells are treated with a stress) confirming that it is a transcriptional regulator. Interestingly, one of these genes that the mutant is unable to induce (gene "Z") is adjacent to "Y" in the genome (downstream), suggesting some sort of relationship between two genes that are contiguous in the genome. Another coincidence (or maybe not...) is that the gene immediately before in the genome ("X") contains a zinc finger domain known as a binding region for DNA and RNA. However, I could not find so far any functional relationship between X and Y.
I believe that some sort of interesting mechanism of regulation is occurring but since this is not a subject that I am very familiar with, I don't know very well how to approach the problem.
Is anyone aware of such gene relationships?
If you're talking about eukaryotic cells, you can do a bit of research about eukaryotic operons to see how common this kind of thing is, and you could try to calculate how likely it is for two zinc finger domain genes to be adjacent. I think you are correct to be suspicious that the knockout might be affecting adjacent gene expression directly. When I see that a knockout mouse has a certain "unexpected" phenotype, I always look to see what the flanking genes are, and quite often these are already implicated in the phenotype. Even if the introduction of Neo cassettes, loxP sites, and the removal of adjacent DNA segments does not alter the expression of the flanking gene, there is also the genetic background issue to think about when working in mice. When you backcross your mutant gene into a pure mouse strain, there will likely never be a crossing over event between your knockout gene and the flanking genes, so you are essentially bringing the flanking genes and all of their SNPs from one background to another.
Hey. Thanks for the answer.
Yes, I am talking about eukaryotic cells (I work with a fungus). I did a little paper research about eukaryotic operons and found some interesting articles. I'll take a look at them.