Transcriptional Interference between Convergent Promoters Caused by Elongation over the Promoter

Callen, Benjamin P.; Shearwin, Keith E.; Egan, J. Barry

doi:10.1016/j.molcel.2004.05.010

Cited by 166 publications

(212 citation statements)

References 31 publications

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“…It is not known whether both polymerases stall during collision and both 'fall off', whether one polymerase (randomly) is rescued from that stalled state by host factors and the other polymerase 'falls off ' [69] or whether a cooperative 'push' from following polymerases can influence the result [70]. We found that interference with transcription from the weak pL promoter of coliphage 186 increases the further its distance from the convergent strong pR promoter [20]. Our modelling [47] confirms the expectation that TI caused by collisions should increase as the distance between two convergent promoters is increased and as their activity is increased.…”

Section: Collisionsmentioning

confidence: 94%

“…Theoretically, an open complex bound at a promoter could act as a roadblock to the progress of an RNAP from another promoter. The in vitro data from Callen et al [20] indicate that the open complex at the coliphage 186 pL promoter does not hinder the progress of an elongating RNAP from pR. It is conceivable that some open complexes are so tightly bound that they could act as roadblocks rather than sitting ducks, but this possibility has not been confirmed.…”

Section: Roadblockmentioning

confidence: 99%

“…Convergent 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 [19,20] (Box 1). 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 [19].…”

Section: What Is the Importance Of Transcriptional Interference?mentioning

confidence: 99%

“…Callen et al [20], 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. The two promoters were variously rearranged to test different models of interference, and mechanisms involving RNA-RNA hybridisation and promoter competition were excluded.…”

Section: Recent Advances In Transcriptional Interferencementioning

confidence: 99%

“…it is slow to 'fire') it can be considered a 'sitting duck', available to be 'hit' and dislodged by the arrival of an elongation complex originating from a strong convergent (or tandem) promoter (Figure 2b). The sitting duck mechanism was proposed by Callen et al [20] to explain the observation in coliphage 186 that interference of the weak lysogenic promoter by the strong lytic promoter disappeared if transcription from the aggressive promoter was terminated before it reached the sitting duck complex at the sensitive promoter. Although their studies involved prokaryotic promoters, the concept could equally well apply in eukaryotic systems, should the transcribing RNA polymerase remove from the DNA either the initiation complex bound at the sensitive promoter or transcription factors associated with it.…”

Section: Sitting Duck Mechanismmentioning

confidence: 99%

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Transcriptional interference – a crash course

2005

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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? What is transcriptional interference?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. 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 [1]; (ii) promoter modification, such as methylation [2]; (iii) hindering the progress of an elongating RNA polymerase (RNAP) by DNA-bound obstacles (other than a second RNAP) [3]; (iv) the inactivation of RNAP by RNA regulators [4]; (v) the insulation of an enhancer site [5]; 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 [6]. 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. the interference with chromosome replication in Saccharomyces cerevisiae as a result of transcription across its site of initiation [7]). 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 [8], chromatin remodelling that promotes intergenic transcription [9] and transcriptional coupling in which a promoter is activated by the activity of an upstream divergent promoter [10].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). 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 whi...

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Section: Collisionsmentioning

confidence: 94%

Section: Roadblockmentioning

confidence: 99%

Section: What Is the Importance Of Transcriptional Interference?mentioning

confidence: 99%

Section: Recent Advances In Transcriptional Interferencementioning

confidence: 99%

Section: Sitting Duck Mechanismmentioning

confidence: 99%

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Transcriptional interference – a crash course

2005

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RNA polymerase pausing at a protein roadblock can enhance transcriptional interference by promoter occlusion

et al. 2019

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Convergent promoters exert transcriptional interference ( TI ) by several mechanisms including promoter occlusion, where elongating RNA polymerases ( RNAP s) block access to a promoter. Here, we tested whether pausing of RNAP s by obstructive DNA ‐bound proteins can enhance TI by promoter occlusion. Using the Lac repressor as a ‘roadblock’ to induce pausing over a target promoter, we found only a small increase in TI , with mathematical modelling suggesting that rapid termination of the stalled RNAP was limiting the occlusion effect. As predicted, the roadblock‐enhanced occlusion was significantly increased in the absence of the Mfd terminator protein. Thus, protein roadblocking of RNAP may cause pause‐enhanced occlusion throughout genomes, and the removal of stalled RNAP may be needed to minimize unwanted TI .

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