Terminating transcription from the strong promoter before it reached the sensitive promoter dramatically reduced interference, indicating a requirement for the passage of a converging RNAP across the sensitive promoter. The two promoters were variously rearranged to test different models of interference, and mechanisms involving RNA–RNA hybridisation and promoter competition were excluded. , in studies of the lysis–lysogeny switch in the temperate coliphage 186, used a single copy LacZ-reporter system demonstrate a 5.6-times reduction in the activity of the weaker lysogenic promoter by the activity of the stronger convergent lytic promoter, which lies 62-bp downstream. Two recent papers underpin the timeliness of a review on TI.Ĭallen et al.
īox 1Recent advances in transcriptional interference The repression of the strong lytic promoter by the immunity repressor prevents the lytic promoter interfering with the convergent lysogenic promoter and so provides the positive autoregulation important in maintaining a stable lysogenic state.
This can be illustrated by the following examples.Ĭonvergent promoters: in the lysis–lysogeny switch of the temperate coliphage 186, the strong lytic promoter reduces the activity of the weaker convergent lysogenic promoter (which lies 62-bp downstream) by 5.6 times ( Box 1). In a genetic network, it appears that TI provides a platform for gene regulation. We first turn our attention to the importance of the natural occurrence of TI. , and Padidam and Cao ) or an unintended manipulation (e.g. in the studies of Proudfoot, Eszterhas et al. Alternatively, they can exist as a result of either an intended experimental manipulation (e.g. In a genome, interfering promoters can exist naturally either as an integral part of a genetic network or as a reflection of the arrival of a transposable element. What is the importance of transcriptional interference? These promoters can be either: (i) convergent promoters directing converging transcripts that overlap for at least part of their sequence ( Figure 1a) (ii) tandem promoters, one upstream of the other but transcribing in the same direction, with their transcripts possibly but not necessarily overlapping ( Figure 1b) or (iii) overlapping promoters, either divergent, convergent or tandem, in which the two RNAP-binding sites share at least a common DNA sequence ( Figure 1c). TI is often asymmetric and results from the existence of two promoters, the strong (aggressive) promoter reducing the expression of the weak (sensitive) promoter ( Figure 1). We also exclude those cases of ‘negative interference’ whereby one transcriptional process, directly and in cis, enhances rather than suppresses a second transcriptional process, such as the fortuitous positioning of a gene within an active chromatin domain, chromatin remodelling that promotes intergenic transcription and transcriptional coupling in which a promoter is activated by the activity of an upstream divergent promoter. the interference with chromosome replication in Saccharomyces cerevisiae as a result of transcription across its site of initiation ). We exclude from our definition of TI examples whereby transcription interferes directly with a cellular activity rather than with transcription associated with cellular activity (e.g. Our definition of TI (see Glossary) excludes the kind of interference that results from the following: (i) the binding of a repressor to its operator overlapping a promoter (ii) promoter modification, such as methylation (iii) hindering the progress of an elongating RNA polymerase (RNAP) by DNA-bound obstacles (other than a second RNAP) (iv) the inactivation of RNAP by RNA regulators (v) the insulation of an enhancer site and (vi) RNA interference (RNAi) in which the product of one transcriptional unit interferes with the half-life of the product of a second transcriptional unit. In this article, we wish to define transcriptional interference (TI) specifically as the suppressive influence of one transcriptional process, directly and in cis on a second transcriptional process.