You’re right; when I wrote “actual sequence” that seemed to imply that the regulatory region for a gene might lie in coding sequences of neighboring genes. If we go with the post-ENCODE definition of a gene (Gerstein et al. 2007), then my statement is definitely inaccurate. I don’t know of any human examples of promoters/enhancers lying in the open reading frame of an adjacent gene (though there might be in viruses, but that’s a different story).

A prominent example of a regulatory enhancer overlapping the (intronic) sequence of another gene is the SNP rs4988235, 13910 bases upstream of the LCT gene, which encodes lactase. The SNP affects LCT expression levels and is highly associated with lactase persistence/lactose intolerance. Lewinsky et al. (2005) have shown that the transcription factor Oct-1 binds directly to the SNP. Yet it’s located in the intron of a different gene, MCM6.

Andro

Thanks for the tip. You’re absolutely right—the SNP lies in the neighboring ANKK1 gene. I mentioned this after the jump. There are several lines of evidence suggesting that the SNP influences expression levels of DRD2, meaning that the SNP might lie in a regulatory region for the DRD2 gene. An overlap between the regulatory region for one gene and the actual sequence of another gene is not uncommon.

The authors refer to the SNP as the “DRD2-TAQ-IA polymorphism.” Most likely this is because the polymorphism was discovered before the ANKK1 gene was. A decent history of the polymorphism is in OMIM.

Andro

You might wish to verify the location of this SNP … it may not reside in the DRD2 gene, but rather in the ANKK1 gene next door.

Fossella J, Green AE, Fan J. Evaluation of a structural polymorphism in the ankyrin repeat and kinase domain containing 1 (ANKK1) gene and the activation of executive attention networks. Cogn Affect Behav Neurosci. 2006 6(1):71-8.