Fig. 6

A model to account for PQS transcriptional correlations. Model summarizes PQS position- and strand-dependent correlations with gene transcription determined from the present work and possible molecular mechanisms to explain these observations. An increase in transcription may be facilitated by the formation of intramolecular G-quadruplex structures between 140–270 bp downstream of the TSS on the sense strand (a), resulting in the release of the antisense strand from Watson-Crick base pairing and enabling easier access of the antisense strand to RNAPII, aiding transcription initiation (b). Formation of G-quadruplex structures in this region may also recruit G-quadruplex DNA-binding proteins (c) which may further stabilize G-quadruplex structures and enhance transcription. Resolution of G-quadruplex structures by BLM and WRN helicases (d) attenuates this transcriptional-activating effect. Transcriptional decrease mediated by PQS downstream of the TSS on both DNA strands may be facilitated by intramolecular G-quadruplex formation, resulting in a biophysical roadblock which prevents the passage of RNAPII and hinders transcript elongation (e). Resolution of G-quadruplex structures by BLM and WRN helicases in this region attenuates the transcriptional-repressing effect of the biophysical roadblock (f). Transcriptional decrease mediated by PQS upstream of the TSS may be recruitment of trans-acting factors that attenuate transcription (g). Resolution of G-quadruplex structures in this region attenuates this transcriptional repressing effect (h)