The yeast actin intron contains a cryptic promoter that can be switched on by preventing transcriptional interference

Irniger, Stefan; Egli, Christoph; Kuenzler, M.; Braus, Gerhard H.

doi:10.1093/nar/20.18.4733

Cited by 30 publications

(20 citation statements)

References 36 publications

(28 reference statements)

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“…Perhaps the highly compact nature of these genomes favours the evolution of convergent transcription to regulate gene expression. In addition, natural examples of TI have been described in bacteria [22,35,41,42] and yeast [21,43,44], but less frequently for higher eukaryotes [23,24,34,45].…”

Section: How Widespread Is Transcriptional Interference?mentioning

confidence: 99%

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: How Widespread Is Transcriptional Interference?mentioning

confidence: 99%

Transcriptional interference – a crash course

2005

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“…An early report suggested a role for TI in repression of a cryptic promoter for the actin locus but it is not clear whether this mechanism is functional in vivo (Irniger et al, 1992). More recent work, however indicates that TI does indeed operate in yeast (Martens et al, 2004).…”

Section: Yeastmentioning

confidence: 99%

Transcriptional interference: an unexpected layer of complexity in gene regulation

Mazo

Hodgson

Petruk

et al. 2007

Journal of Cell Science

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Much of the genome is transcribed into long untranslated RNAs, mostly of unknown function. Growing evidence suggests that transcription of sense and antisense untranslated RNAs in eukaryotes can repress a neighboring gene by a phenomenon termed transcriptional interference. Transcriptional interference by the untranslated RNA may prevent recruitment of the initiation complex or prevent transcriptional elongation. Recent work in yeast, mammals, and Drosophila highlights the diverse roles that untranslated RNAs play in development. Previously, untranslated RNAs of the bithorax complex of Drosophila were proposed to be required for its activation. Recent studies show that these untranslated RNAs in fact silence Ultrabithorax in early embryos, probably by transcriptional interference.

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“…The Promoter Activity of the Lazarus Element-While there are a number of examples of cryptic promoters, most appear to function in expressing an alternative product of the specific gene (27)(28)(29)(30)(31)(32). However, results of S1 nuclease and RNase protection analysis of the RNA of human cells (11), transfected mouse cells (6), and transgenic mice (21) indicate that levels of Lazarus promoter-initiated RNA could not represent more than a small percentage of the normal K18 signal.…”

Section: The Lazarus Promoter Can Direct Expression Of a Heterologousmentioning

confidence: 99%

A Regulatory Element of the Human Keratin 18 Gene with AP-1-dependent Promoter Activity

Rhodes

Oshima

1998

Journal of Biological Chemistry

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The human keratin 18 (K18) gene is expressed in a restricted but diverse subset of differentiated epithelial tissues and carcinomas. The 10-kilobase pair K18 gene contains all of the genetic information necessary for tissue-specific, copy number-dependent and integration site-independent expression in transgenic mice. We identified a 100-base pair regulatory element that activates the K18 proximal promoter in the presence of the previously identified first intron enhancer. Deletion of the element greatly diminished K18 expression. This regulatory element also has cryptic, AP-1-dependent promoter activity in the absence of the normal promoter, which results in 10 -40-fold higher levels of K18 RNA expression in transgenic mice. The high activity of this cryptic promoter is dependent upon the first intron enhancer. These experiments define interactive regulatory regions of the K18 gene that modulate expression in diverse epithelial cell types and identify an unusual regulatory element with promoter activity that may be useful for high level heterologous gene expression in transgenic animals.

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The yeast actin intron contains a cryptic promoter that can be switched on by preventing transcriptional interference

Cited by 30 publications

References 36 publications

Transcriptional interference – a crash course

Transcriptional interference – a crash course

Transcriptional interference: an unexpected layer of complexity in gene regulation

A Regulatory Element of the Human Keratin 18 Gene with AP-1-dependent Promoter Activity

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