Long-range promoter-enhancer contacts are conserved during evolution and contribute to gene expression robustness

Alexandre Laverré, Eric Tannier & Anamaria Necsulea

Gene expression is regulated through complex molecular interactions, involving cis-acting elements that can be situated far away from their target genes. Data on long-range contacts between promoters and regulatory elements is rapidly accumulating. However, it remains unclear how these regulatory relationships evolve and how they contribute to the establishment of robust gene expression profiles. Here, we address these questions by comparing genome-wide maps of promoter-centered chromatin contacts in mouse and human. We show that there is significant evolutionary conservation of cis-regulatory landscapes, indicating that selective pressures act to preserve regulatory element sequences and their interactions with target genes. The extent of evolutionary conservation is remarkable for long-range promoter-enhancer contacts, illustrating how the structure of regulatory interactions constrains large-scale genome evolution. Notably, we show that the evolution of cis-regulatory landscapes, measured in terms of distal element sequences, synteny or contacts with target genes, is tightly linked to gene expression evolution.

The data generated in this project are all available below:

• Supplemental Dataset 1 (tar.gz archive)
• Supplemental Dataset 2 (tar.gz archive)
• Supplemental Dataset 3 (tar.gz archive)
• Supplemental Dataset 4 (tar.gz archive)
• Supplemental Dataset 5 (tar.gz archive)
• Supplemental Dataset 6 (tar.gz archive)
• Supplemental Dataset 7 (tar.gz archive)
• Supplemental Dataset 8 (tar.gz archive)
• Supplemental Dataset 9 (tar.gz archive)
• Supplemental Table 1
• Supplemental Table 2
• Supplemental Table 3
• Supplemental Table 4
• Supplemental Table 5