Biophysics Department, Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, 119435, Russia.
Bioessays. 2019 Sep;41(9):e1900091. doi: 10.1002/bies.201900091. Epub 2019 Aug 5.
Here, the emerging data on DNA G-quadruplexes (G4s) as epigenetic modulators are reviewed and integrated. This concept has appeared and evolved substantially in recent years. First, persistent G4s (e.g., those stabilized by exogenous ligands) were linked to the loss of the histone code. More recently, transient G4s (i.e., those formed upon replication or transcription and unfolded rapidly by helicases) were implicated in CpG island methylation maintenance and de novo CpG methylation control. The most recent data indicate that there are direct interactions between G4s and chromatin remodeling factors. Finally, multiple findings support the indirect participation of G4s in chromatin reshaping via interactions with remodeling-related transcription factors (TFs) or damage responders. Here, the links between the above processes are analyzed; also, how further elucidation of these processes may stimulate the progress of epigenetic therapy is discussed, and the remaining open questions are highlighted.
本文综述并整合了 DNA 四链体（G4s）作为表观遗传调节剂的新兴数据。这一概念近年来已经有了实质性的发展。首先，稳定的 G4s（例如，由外源配体稳定的 G4s）与组蛋白密码的丢失有关。最近，瞬态 G4s（即在复制或转录过程中形成并迅速由解旋酶解旋的 G4s）被牵连到 CpG 岛甲基化维持和从头甲基化控制中。最新的数据表明，G4s 与染色质重塑因子之间存在直接相互作用。最后，多项发现支持 G4s 通过与重塑相关的转录因子（TFs）或损伤应答物相互作用间接参与染色质重塑。本文分析了上述过程之间的联系；此外，还讨论了进一步阐明这些过程如何促进表观遗传治疗的进展，并强调了仍然存在的问题。
