Diversity of core promoter elements comprising human bidirectional promoters

Abstract

Background: Bidirectional promoters lie between adjacent genes, which are transcribed from opposite strands of DNA. The functional mechanisms underlying the activation of bidirectional promoters are currently uncharacterised. To define the core promoter elements of bidirectional promoters in human, we mapped motifs for TATA, INR, BRE, DPE, INR, as well as CpG-islands.

Results: We found a consistently high correspondence between C+G content, CpG-island presence and an average expression level increasing the median level for all genes in bidirectional promoters. These CpG-rich promoters showed discrete initiation patterns rather than broad regions of transcription initiation, as are typically seen for CpG-island promoters. CpG-islands encompass both TSSs within bidirectional promoters, providing an explanation for the symmetrical co-expression patterns of many of these genes. In contrast, TATA motifs appear to be asymmetrically positioned at one TSS or the other.

Conclusion: Our findings demonstrate that bidirectional promoters utilize a variety of core promoter elements to initiate transcription. CpG-islands dominate the regulatory landscape of this group of promoters.

Figure 1

TATA motifs in bidirectional promoters. (A) TATA motifs were mapped in the 500 bp regions upstream of TSSs and 100 bp downstream for bidirectional promoters and nonbidirectional promoters. (B) The percentage of genes with TATA motifs as measured at the functional position at -30 bp upstream of the TSS. A range from -44 to -20 was used to accommodate some error in the annotations. The full promoter regions from positions -500 to +100 contains many occurrences of TATA motifs, however based on the characterized mechanism of the TATA motif, these are false positive predictions.

Figure 2

CPEs in bidirectional promoters. Core promoter elements include TATA, INR, BRE, and CCAAT motifs (A-D). Elements were mapped in the full promoter region. A dashed line at position +1 indicates the TSS. Bidirectional promoters are plotted in blue for negative and positive strand genes. Nonbidirectional promoters are plotted in red.

Figure 3

CG nucleotide bias in bidirectional promoters. (A) C+G content plotted as a histogram of the dinucleotide density. Plots are stacked with bidirectional promoters on top and Tail_to_tail regions on the bottom. (B) The CpG-island content of these same categories of promoters.

Figure 4

Expression profiles of CpG-island promoters. Expression profiles for 17 blood-related samples were analyzed. The data are divided into (A) bidirectional promoters with CpG-islands (B) nonbidirectional promoters with CpG-islands (C) nonbidirectional promoters without CpG-islands. Individual columns in the plot represent genes, whereas cells and tissues are on the vertical axis. Expression is relative to the median value from >16,000 genes available in the human GNF dataset. Red indicates expression above the median, green is below, black is equivalent.

Figure 5

RNA POLII sequence tags at bidirectional promoters. (A) Data are separated into negative and positive strand genes. Bidirectional promoters are plotted in blue, whereas nonbidirectional promoters are in red. RNA POLII tags are averaged by the total number of promoters. (B) Pie charts of the promoter elements in each dataset. CpG-island = CpG, Any core promoter element = CPE.

Figure 6

Assymmetry of TATA motifs in bidirectional promoters. TATA motifs present at the left and right TSS are plotted separately. When a TATA-motif was detected, the functional TATA position was assessed at the other TSS. Only one gene pair showed a TATA at both positions. Other CPE motifs were mapped to explain regulatory control in the absence of the TATA motif.

Figure 7

CAGE tags at bidirectional promoters. CAGE tags were mapped according to their sequence identity on the negative or positive strands. Within a 20 bp regions surrounding the TSS, one dominant peak is detected for each strand. CAGE tags represent an average of the number of promoters in the analysis.