G-quadruplexes are nucleic
acid sequences that are rich in guanine and are capable of forming a
four-stranded structure through Hoogsteen hydrogen bonding. G-rich regions
capable of forming G-quadruplex (G4) structures are highly concentrated near
promoters and transcription start sites
suggesting a role in gene
regulation. They are less often found on the template strand than on the
non-template strand where they either inhibit or enhance transcription,
respectively. However, their potential role in enhancers and in other distal
regulatory elements has not been assessed
yet. Here we show that DNAse
hypersensitive (DHS) cis regions with regulatory roles are also enriched in Gs
and their G-content correlate with that of their respective promoters. Besides
local G4s, the distal cis regions have the capability to form G-quadruplexes
together with the promoters, each contributing half of a G4 only. This model is
supported more for the non-template strand and we hypothesised that the G4
forming capability of the promoter and the enhancer non-template strand could facilitate
their binding together and making the DHS regions accessible for the
transcription factory. As G4s are targets of intense research and cancer drug
development, we anticipate that our model will induce experimentalists to
verify it in the lab and contribute to a better understanding of such a basic
phenomenon as gene expression regulation.