Trends in Genetics
Volume 21, Issue 6, June 2005, Pages 339-345
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Transcriptional interference – a crash course

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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?

Section snippets

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)

What is the importance of transcriptional interference?

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. Alternatively, they can exist as a result of either an intended experimental manipulation (e.g. in the studies of Proudfoot 11, 12, 13, Eszterhas et al. [14], and Padidam and Cao [15]) or an unintended manipulation (e.g. the insertion of foreign cloned DNA 16, 17, 18). We first turn our attention to the importance of the natural

How widespread is transcriptional interference?

Nasser et al. [35] have suggested that the use of promoter interactions as a mechanism of gene regulation co-evolved with factor-dependent regulation or that there was a primordial RNA-polymerase-dependent homeostatic regulation and an extra level of control by transcription factors has evolved during the course of evolution. Examples of TI as a means of gene regulation are common in the genomes of ‘extrachromosomal’ elements such as bacteriophages 19, 36, 37, 38, transposable elements [39],

How does transcriptional interference work?

Although reports of TI in both prokaryotes and eukaryotes have been published over many years, few studies have addressed the underlying mechanisms. The earlier publications that have influenced our understanding of the mechanisms involved are in vivo studies on convergent promoters by Ward and Murray [61], an in vitro study on promoters arranged both convergently and in-tandem by Horowitz and Platt [62] and, in particular, the in vivo study of a convergent promoter pair by Elledge and Davis

Outlook

Eszterhas et al. [14] set out to obtain some systematic understanding of the mechanisms operating in TI in mouse leukemic cells. They studied the expression of two reporter genes each bounded by a CMV promoter and an SV40 large T antigen polyadenylation signal. They studied all arrangements (convergent, divergent and tandem) in both orientations and integrated them at two different chromosomal loci and concluded that ‘the two transcriptional units interfere with each other in ways that cannot

Concluding remarks

TI occurs in most genomes and has probably persisted during evolution because of its potential use in regulating gene expression. A variety of mechanisms have been identified and successfully studied, at least in simple systems. A major aim for the future is to exploit mathematical modelling to characterize TI, and a major issue to explore further is the fate of an elongating RNAP when it meets a DNA-bound obstacle, either moving or stationary.

Acknowledgements

We wish to acknowledge the help of the other members of the Egan laboratory and of Kim Sneppen (NORDITA) in writing this article. Research in the Egan laboratory was funded by the Australian Research Council and the National Institutes of Health.

Glossary

Transcriptional interference:
the suppressive influence of one transcriptional process, directly and in cis, on a second transcriptional process.
Promoter competition:
occupation by RNA polymerase (RNAP) of one promoter directly precludes RNA-polymerase binding at a second promoter. This can be extended to include competition between two promoters for the same enhancer.
Occlusion:
transcription across a promoter from an external promoter transiently precludes its occupation by RNAP and/or associated

References (74)

  • A.F. Smit

    Interspersed repeats and other mementos of transposable elements in mammalian genomes

    Curr. Opin. Genet. Dev.

    (1999)
  • P. Nigumann

    Many human genes are transcribed from the antisense promoter of L1 retrotransposon

    Genomics

    (2002)
  • R.W. Simons

    Three promoters near the termini of IS10: pIN, pOUT, and pIII

    Cell

    (1983)
  • S. Adhya et al.

    Promoter occlusion: transcription through a promoter may inhibit its activity

    Cell

    (1982)
  • R. Gafny

    Isolated P2 rRNA promoters of Escherichia coli are strong promoters that are subject to stringent control

    J. Mol. Biol.

    (1994)
  • K. Sneppen

    A mathematical model for transcriptional interference by RNA polymerase traffic in Escherichia coli

    J. Mol. Biol.

    (2005)
  • A. Marin

    Short-range compositional correlation in the yeast genome depends on transcriptional orientation

    Gene

    (2004)
  • S. Cawley

    Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs

    Cell

    (2004)
  • D.F. Ward et al.

    Convergent transcription in bacteriophage lambda: interference with gene expression

    J. Mol. Biol.

    (1979)
  • O.R. Choi et al.

    Developmental regulation of β-globin gene switching

    Cell

    (1988)
  • S. Liang

    Activities of constitutive promoters in Escherichia coli

    J. Mol. Biol.

    (1999)
  • E. Bateman et al.

    Promoter occlusion during ribosomal RNA transcription

    Cell

    (1988)
  • J. Roberts et al.

    Mfd, the bacterial transcription repair coupling factor: translocation, repair and termination

    Curr. Opin. Microbiol.

    (2004)
  • A.K. Nagaich

    Rapid periodic binding and displacement of the glucocorticoid receptor during chromatin remodeling

    Mol. Cell

    (2004)
  • V. Epshtein

    Transcription through the roadblocks: the role of RNA polymerase cooperation

    EMBO J.

    (2003)
  • K.M. Wassarman

    RNA regulators of transcription

    Nat. Struct. Mol. Biol.

    (2004)
  • G. Meister et al.

    Mechanisms of gene silencing by double-stranded RNA

    Nature

    (2004)
  • S. Tanaka

    Transcription through the yeast origin of replication ARS1 ends at the ABFI binding site and affects extrachromosomal maintenance of minichromosomes

    Nucleic Acids Res.

    (1994)
  • I. Cajiao

    Bystander gene activation by a locus control region

    EMBO J.

    (2004)
  • M.L. Opel

    The effects of DNA supercoiling on the expression of operons of the ilv regulon of Escherichia coli suggest a physiological rationale for divergently transcribed operons

    Mol. Microbiol.

    (2001)
  • N.J. Proudfoot

    Transcriptional interference and termination between duplicated α-globin gene constructs suggests a novel mechanism for gene regulation

    Nature

    (1986)
  • I.H. Greger

    Transcriptional interference perturbs the binding of Sp1 to the HIV-1 promoter

    Nucleic Acids Res.

    (1998)
  • E.M. Prescott et al.

    Transcriptional collision between convergent genes in budding yeast

    Proc. Natl. Acad. Sci. U. S. A.

    (2002)
  • S.K. Eszterhas

    Transcriptional interference by independently regulated genes occurs in any relative arrangement of the genes and is influenced by chromosomal integration position

    Mol. Cell. Biol.

    (2002)
  • M. Padidam et al.

    Elimination of transcriptional interference between tandem genes in plant cells

    Biotechniques

    (2001)
  • A.J. Thompson et al.

    Tetracycline-dependent activation of an upstream promoter reveals transcriptional interference between tandem genes within T-DNA in tomato

    Plant Mol. Biol.

    (1997)
  • I.B. Dodd et al.

    Action at a distance in CI repressor regulation of the bacteriophage 186 genetic switch

    Mol. Microbiol.

    (2002)
  • Cited by (0)

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