Termination of transcription defines the actual end of a gene and is mediated by signals involved in 3' end processing of the nascent RNA transcript as well as additional downstream elements. Deletion of these terrnination signals can lead to interference between adjacent genes resulting in impairment of expression of the downstream gene. This suggests a key role for termination in the regulation of gene expression. Interference has been observed in a number of genetic systems and represents a serious problem in the design of vectors for gene therapy. In the first year of my PhD, I have investigated the biological role of interference by studying the effect of placing two genes (transcribed by RNA polymerase II) in close proximity in a chromosomal context. Using such constructions I have studied the molecular basis of this mechanism by directly characterising the effect of interference on the binding of transcription factors to the downstream positioned gene.
I now intend to define more completely the general significance of this mechanism in genetically tractable yeast systems.