A model of G4 DNA-mediated stimulation of transcription. Double-stranded DNA is denatured locally during transcription, forming a transcription bubble and exposing the template strand for nascent RNA synthesis (A, top). As RNAP II machinery (gray dashed box) moves along the template strand, the bubble moves with it, and the DNA rewinds to form the duplex behind the bubble (A, bottom). For the PG4MD500-positive genes, the transient separation of the duplex DNA during transcription and transcription-derived negative supercoiling considerably increases the opportunities for the formation of G4 DNA. Such high-order structures are extremely stable, and thus, probably block rehybridization with the complementary strand, holding the structure open and thereby enabling a higher rate of transcription (B). For the same reason, the presence of high numbers of PG4MD500 can help maintain the initial region of the transcript unpaired, which could facilitate the reinitiation of transcription (black dashed box) and also contribute to a higher level of transcription (B, bottom). The presence of PG4Ms in the template strand may hinder the progression of RNAP II. However, the intrinsic asymmetric distribution of PG4Ms between strands in the D500 region (PG4MD500cod > PG4MD500tem, represented in gray and black, respectively; see also Fig. 4) achieves a balance and minimizes the negative effects.
