Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova 35131, Italy.
Department of Molecular Medicine, University of Padova, Padova 35131, Italy.
Nucleic Acids Res. 2022 Feb 22;50(3):1370-1381. doi: 10.1093/nar/gkab1274.
G-quadruplex (G4) structures that can form at guanine-rich genomic sites, including telomeres and gene promoters, are actively involved in genome maintenance, replication, and transcription, through finely tuned interactions with protein networks. In the present study, we identified the intermediate filament protein Vimentin as a binder with nanomolar affinity for those G-rich sequences that give rise to at least two adjacent G4 units, named G4 repeats. This interaction is supported by the N-terminal domains of soluble Vimentin tetramers. The selectivity of Vimentin for G4 repeats versus individual G4s provides an unprecedented result. Based on GO enrichment analysis performed on genes having putative G4 repeats within their core promoters, we suggest that Vimentin recruitment at these sites may contribute to the regulation of gene expression during cell development and migration, possibly by reshaping the local higher-order genome topology, as already reported for lamin B.
G-四链体（G4）结构可以在富含鸟嘌呤的基因组位点形成，包括端粒和基因启动子，通过与蛋白质网络的精细相互作用，积极参与基因组的维持、复制和转录。在本研究中，我们鉴定了中间丝蛋白波形蛋白（Vimentin）作为一种与富含鸟嘌呤的序列结合的蛋白，这些序列至少产生两个相邻的 G4 单元，称为 G4 重复。这种相互作用得到可溶性 Vimentin 四聚体的 N 端结构域的支持。波形蛋白对 G4 重复与单个 G4 的选择性提供了一个前所未有的结果。基于对核心启动子中具有潜在 G4 重复的基因进行的 GO 富集分析，我们认为 Vimentin 在这些位点的募集可能有助于细胞发育和迁移过程中基因表达的调节，可能通过重塑局部高级基因组拓扑结构，正如已经报道的核纤层蛋白 B 一样。
