The dual lives of bidirectional promoters

Abstract

The sequencing of the human genome led to many insights into gene organization and structure. One interesting observation was the high frequency of bidirectional promoters characterized by two protein encoding genes whose promoters are arranged in a divergent or "head-to-head" configuration with less than 2000 base pairs of intervening sequence. Computational estimates published by various groups indicate that nearly 10% of the coding gene promoters are arranged in such a manner and the extent of this bias is a unique feature of mammalian genomes. Moreover, as a class, head-to-head promoters appear to be enriched in specific categories of gene function. Here we review the structure, composition, genomic properties and functional classifications of genes controlled by bidirectional promoters and explore the biological implication of these features. This article is part of a Special Issue entitled: Chromatin in time and space.

Figure 1. Schematic of a bidirectional promoter

Example of a bidirectional promoter for divergently transcribed genes (head to head configuration) PALB2 and DCTN5 with TSS occurring within 2000 bp of each other. Illustrated is the tag density profile for the binding of the C-terminal binding protein (CtBP) at a bidirectional promoter.

Figure 2. Size distribution of bidirectional promoters in the human genome

Histogram representing the size distribution of bidirectional promoters for genes (head-to-head orientation) containing TSS which occur within 2000 bp. X-axis represents an interval of 75 bp for each bin. Y-axis represents the frequency of events (bidirectional promoters) that fall into each bin. The bidirectional promoters were retrieved based on the UCSC refgene List (HG19): http://hgdownload.cse.ucsc.edu/goldenPath/hg19/database/refGene.txt.gz). A gene was determined to have a bidirectional promoter if the distance bewteen its TSS (transcriptional start site) and closest divergently transcribed TSS is less than 2000 bp in length.

Figure 3. Size and functional distribution of bidirectional promoters in the human genome

(a) Distribution of genes with bidirectional promoters according to length (bp). The majority of bidirectional promoters occur within 500 bp of the TSS of genes (head-to-head orientation). The number of genes stated is for all genes with a divergent head-to-head orientation separated by <2000 bp. (b) Gene ontology and functional distribution of genes with bidirectional promoters according to length (bp) represented in percentage of total bidirectional promoter in that category. Gene ontology analyses were performed using the GoMiner web-based software [23,35].