An Abundance of Bidirectional Promoters in the Human Genome

Abstract

The alignment of full-length human cDNA sequences to the finished sequence of the human genome provides a unique opportunity to study the distribution of genes throughout the genome. By analyzing the distances between 23,752 genes, we identified a class of divergently transcribed gene pairs, representing more than 10% of the genes in the genome, whose transcription start sites are separated by less than 1000 base pairs. Although this bidirectional arrangement has been previously described in humans and other species, the prevalence of bidirectional gene pairs in the human genome is striking, and the mechanisms of regulation of all but a few bidirectional genes are unknown. Our work shows that the transcripts of many bidirectional pairs are coexpressed, but some are antiregulated. Further, we show that many of the promoter segments between two bidirectional genes initiate transcription in both directions and contain shared elements that regulate both genes. We also show that the bidirectional arrangement is often conserved among mouse orthologs. These findings demonstrate that a bidirectional arrangement provides a unique mechanism of regulation for a significant number of mammalian genes

A highly conserved proapoptotic gene, IKIP, located next to the APAF1 gene locus, is regulated by p53

“…Thereby both common but also mutually exclusive regulation can be envisaged, the latter especially since the described promoter region of APAF1 extends into the transcribed region of IKIP. A recent survey of transcribed sequences in the human genome has revealed that bidirectional promoters occur rather frequently; 22 however, the mechanisms of regulation of all but a few bidirectional genes are unknown. The same study shows that the transcripts of many bidirectional pairs are coexpressed, whereas some are antiregulated, and further that many of the promoter segments between two bidirectional genes contain shared elements that regulate both genes.…”

New meaning in the message: Noncoding RNAs and their role in retinal development

“…Large-scale microarray analysis in both yeast and humans indicates that such genes are often coregulated, as might be expected given that they share common 5Ј cis-regulatory sequences (Cohen et al, 2000;Trinklein et al, 2004). A surprising finding to emerge from large-scale cDNA sequencing efforts is that noncoding, mRNA-like transcripts are also often transcribed in a head-to-head, or discordant, orientation with protein-coding genes (Carninci et al, 2005;Katayama et al, 2005).…”

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

“…The same is true for their paralogs DUOX2/DUOXA2. Bidirectionally promoted gene pairs represent ~10% of all transcriptional units and have a higher probability of coordinated expression than random pairs of genes (95). Accordingly, expression of DUOX1/DUOXA1 and DUOX2/DUOXA2 in airway epithelial cells or thyrocytes have been found to be closely coordinated (90,93).…”