Transcriptional interference--a crash course

Abstract

The term "transcriptional interference" (TI) is widely used but poorly defined in the literature. There are a variety of methods by which one can interfere with the process or the product of transcription but the term TI usually refers to the direct negative impact of one transcriptional activity on a second transcriptional activity in cis. Two recent studies, one examining Saccharomyces cerevisiae and the other Escherichia coli, clearly show TI at one promoter caused by the arrival of a transcribing complex initiating at a distant promoter. TI is potentially widespread throughout biology; therefore, it is timely to assess exactly its nature, significance and operative mechanisms. In this article, we will address the following questions: what is TI, how important and widespread is it, how does it work and where should we focus our future research efforts?

Figure 1

Promoter arrangements that can lead to transcriptional interference (TI). TI can arise as a result of several different promoter arrangements: (a) convergent promoters, such as the coliphage 186 lytic and lysogenic promoters [20]; (b) tandem promoters, for example, the promoters of yeast SRG1 and SER3 [21]; (c) overlapping promoters, such as the E. coli aroP P1 and P3 promoters [22]. Although the example of overlapping promoters shown in (c) shows a divergent promoter pair, both tandem and convergent promoter pairs can also overlap. RNAP-binding sites are indicated by grey boxes, the starting points (+1) of transcription are shown as black arrows and transcripts as green arrows.

Figure 2

Mechanisms of transcriptional interference (TI). Five possible mechanisms by which TI can occur are: (a) promoter competition; (b) sitting duck interference; (c) occlusion; (d) collision; and (e) roadblock. For the example shown here where a strong (aggressive) promoter pA is oriented convergently to a weak (sensitive) promoter pS, all five mechanisms are possible. For promoters arranged in tandem, all mechanisms except the collision mechanism [shown in (d)] can apply. When the promoters are arranged divergently, only the promoter competition mechanism shown in (a) can apply, but only when the promoters are also overlapping.