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? 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...

A de novo originated gene depresses budding yeast mating pathway and is repressed by the protein encoded by its antisense strand

“…MDF1) transcripts could be completely abolished by overexpressed ADF1 (Figure 2B). Because the overexpressed ADF1 on the plasmid does not physically overlap with the chromosomal MDF1, transcription interference [4] is not a probable cause. This transcriptional suppression is instead probably due to the RNA or protein of ADF1 present in the cells.…”

“…However, in Saccharomyces cerevisiae, components of the RNAi machinery are absent [3], and antisense repression can be mediated by transcription interference (TI) or histone deacetylation. TI was thought to be an unavoidable suppressive consequence of two convergent promoters directing transcripts that overlap for at least part of their sequences [4]. But in the case of PHO84, the sense gene is regulated by accumulation of antisense RNAs, which leads to targeted histone deacetylation and the silencing of sense transcription [5].…”

The Fur homologue BosR requires Arg39 to activate rpoS transcription in Borrelia burgdorferi and thereby direct spirochaete infection in mice

“…6, bottom). In this model, the spirochaete employs transcriptional interference (Palmer et al, 2009(Palmer et al, , 2011Shearwin et al, 2005) to control (i.e. close down) synthesis of the short rpoS transcript.…”

Genomic Imprinting and Epigenetic Control of Development

“…Both Airn and Kcnq1ot1 have transcriptional start sites within introns of protein-coding genes (Igf2r and Kcnq1, respectively) and are transcribed in the antisense direction. The premature transcriptional termination of Airn ncRNA before the Igf2r promoter results in paternal Igf2r expression , suggesting that Airn functions, at least partially, through transcriptional interference (Shearwin et al 2005). However, Airn and Kcnq1ot1 transcription traverses only a subset of genes, which they repress.…”