Comparative genetic analysis of the transcriptional regulatory DNA of the oxytocin and vasopressin genes

Abstract

The regulation of gene transcription is central to biology, but poorly understood. I chose sequence comparisons to identify regulatory DNA of the oxytocin and vasopressin genes. I used transgenic mice to show that the regulation is conserved between the mouse genes and their Fugu orthologues, isotocin and vasotocin, but could not detect informative non-coding sequence similarity between the mouse and Fugu, or even mouse and human genes. I postulated that under neutral evolution, transcription factor binding sites would be retained within the enhancer as a whole, but might be gained and lost at positions within the enhancer. I used "comparative gel-shifts" to identify transcription factor binding sites that were indeed a??conserveda?? in this way. These results suggest that "grammar" - in at least some enhancers - is very flexible, that enhancers might be very "evolvable" compared to coding sequences, and that a conceptually similar approach to might be used in genome annotation.