The ability of genomic DNA to adopt non-canonical secondary structures known as G-quadruplexes (G4s) under physiological conditions has been recognized for its potential regulatory function of various biological processes. Among those, transcription has recently emerged as a key process that can be heavily affected by G4 formation, particularly when these structures form at gene promoters. While the presence of G4s within gene promoters has been traditionally associated with transcriptional inhibition, in a model whereby G4s act as roadblocks to polymerase elongation, recent genomics experiments have revealed that the regulatory role of G4s in transcription is more complex than initially anticipated. Indeed, earlier studies linking G4-formation and transcription mainly relied on small-molecule ligands to stabilize and promote G4s, which might lead to disruption of protein–DNA interactions and local environments and, therefore, does not necessarily reflect the endogenous function of G4s at gene promoters. There is now strong evidence pointing toward G4s being associated with transcriptional enhancement, rather than repression, through multifaceted mechanisms such as recruitment of key transcriptional proteins, molding of chromatin architecture, and mode of phase separation.

中文翻译：

---

多分子 G-四链体在转录调控和染色质组织中的新作用


基因组 DNA 在生理条件下采用称为 G-四链体 （G4） 的非经典二级结构的能力因其对各种生物过程的潜在调节功能而得到认可。其中，转录最近已成为一个关键过程，可能会受到 G4 形成的严重影响，尤其是当这些结构在基因启动子处形成时。虽然基因启动子中 G4s 的存在传统上与转录抑制有关，但在 G4s 充当聚合酶延伸障碍的模型中，最近的基因组学实验表明，G4s 在转录中的调节作用比最初预期的要复杂。事实上，将 G4 形成和转录联系起来的早期研究主要依赖于小分子配体来稳定和促进 G4s，这可能导致蛋白质-DNA 相互作用和局部环境的破坏，因此，不一定反映 G4s 在基因启动子处的内源性功能。现在有强有力的证据表明，G4s 通过多方面的机制（例如关键转录蛋白的募集、染色质结构的塑造和相分离模式）与转录增强相关，而不是抑制。