Fig. 3

Effects of eG4 dynamics on transcription. A The promoter binds to various transcription factors through eG4 folding to regulate gene transcription. B Folding of template chain eG4s leads to the stalling of RNA polymerase and reduces the level of transcription. C Folding of non-template chain eG4s has two effects on transcription. Folding of eG4s improves the structural stability of the R-loop formed by template chain DNA and RNA, thereby reducing transcription levels. In addition, folding of eG4s also maintains the separation of template chain and non-template chain, thereby promoting transcription reinitiation. D Folding of heterozygous eG4s, consisting of RNA and non-template chain DNA, leads to advanced transcription termination and decreased transcription levels. E DNMT methylates DNA using CpG as a target, and transcription of the methylated DNA is inhibited (left). When eG4s are folded on the CpG island, they bind DNMT and inhibit its activity, thereby reducing the level of methylation and avoiding transcription inhibition (right). F Promoter eG4 folding also indirectly regulates transcription levels. The REST-LSD1 complex is recruited to eG4s in an NME2- or TRF2-dependent manner. Histones of nearby nucleosomes are demethylated by REST-LSD1, resulting in transcription repression