Trends in Genetics
ReviewFunctional consequences of bidirectional promoters
Section snippets
Bidirectionality is an inherent feature of promoters
During the past decade, genomic research has focused on protein-coding genes. However, recent studies have revealed a myriad of non-coding transcripts in different organisms 1, 2. Whereas protein-coding transcription represents the output of less than 2% of the human genome, more than 70% of the genome is transcribed [3]. The unexpected level of transcriptome complexity has led to the suggestion that non-coding RNAs (ncRNAs) comprise a previously hidden layer of genomic programming and that
Different technologies demonstrate the bidirectionality of promoters
The extent of ncRNA transcription has been investigated using different approaches, including measurements of steady-state RNA levels 13, 14, 17, 18, 21, 22, 23, 24, RNA polymerase activity [25] and nascent RNAs associated with RNA polymerase II [26]. These studies have resulted in a catalog of non-coding transcripts near protein-coding genes and have revealed both protein/non-coding and non-coding/non-coding bidirectional transcription (Figure 1).
A large body of evidence for promoter
Architecture of bidirectional promoters
A promoter can be defined as a region of DNA that directs the transcription of a downstream unit 31, 32. To understand how bidirectional transcription works, it is important to study the role that chromatin structure plays in the assembly of the transcription machinery and how chromatin is dynamically regulated 33, 34, 35, 36.
Functional consequences of pervasive transcription at bidirectional promoters
When several transcripts are produced from the same promoter, the promoter must act as a regulatory unit to couple their transcription. The effect of this transcription on gene activity (local or distal) could be mediated by either the transcription process itself or by the produced transcripts. The consequences of ncRNA transcription from a bidirectional promoter thus depend on transcript length, sequence and stability. Although there are an increasing number of case studies demonstrating that
Concluding remarks and future perspectives
Much of the increased phenotypic complexity of higher eukaryotes is thought to arise from gene regulation rather than from an increase in protein-coding gene numbers 93, 94, 95. In addition to regulation mediated by distantly acting ncRNAs, expression of ncRNAs close to gene promoter regions provides a convenient means to regulate and fine-tune gene expression levels locally by exploiting shared chromatin, shared sequence, or sequence complementarity. Although some of the non-coding
Acknowledgements
We thank Raeka Aiyar, Wolfgang Huber, Julien Gagneur, Zhenyu Xu and Joël Savard for critical comments on the manuscript. This work was supported by grants to LMS from the National Institutes of Health and the Deutsche Forschungsgemeinschaft. VP is supported by an EMBO postdoctoral Fellowship.
Glossary
- Backtracked polymerase
- RNA polymerase II molecules that have moved backwards on the DNA template, leaving a misaligned 3′ end of the RNA that requires the aid of accessory factors to resume elongation.
- Bidirectional promoter
- a genomic region of DNA that initiates transcription in both orientations. Different definitions of bidirectional promoters have been applied in diverse studies. For example, in yeast, transcripts were considered to originate from a bidirectional promoter when their start
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These authors contributed equally to this work.