Department of Molecular Medicine, University of Padua, Padua, Italy.
Division of Molecular Biology, Biomedical Center, Faculty of Medicine, LMU Munich, Martinsried, Germany.
Nat Commun. 2021 Jun 23;12(1):3885. doi: 10.1038/s41467-021-24198-2.
Cell identity is maintained by activation of cell-specific gene programs, regulated by epigenetic marks, transcription factors and chromatin organization. DNA G-quadruplex (G4)-folded regions in cells were reported to be associated with either increased or decreased transcriptional activity. By G4-ChIP-seq/RNA-seq analysis on liposarcoma cells we confirmed that G4s in promoters are invariably associated with high transcription levels in open chromatin. Comparing G4 presence, location and transcript levels in liposarcoma cells to available data on keratinocytes, we showed that the same promoter sequences of the same genes in the two cell lines had different G4-folding state: high transcript levels consistently associated with G4-folding. Transcription factors AP-1 and SP1, whose binding sites were the most significantly represented in G4-folded sequences, coimmunoprecipitated with their G4-folded promoters. Thus, G4s and their associated transcription factors cooperate to determine cell-specific transcriptional programs, making G4s to strongly emerge as new epigenetic regulators of the transcription machinery.
细胞身份由细胞特异性基因程序的激活来维持,这些程序受表观遗传标记、转录因子和染色质组织的调节。细胞中的 DNA G-四链体 (G4)-折叠区域与转录活性的增加或减少有关。通过对脂肪肉瘤细胞进行 G4-ChIP-seq/RNA-seq 分析,我们证实启动子中的 G4s 始终与开放染色质中的高转录水平相关。将脂肪肉瘤细胞中 G4 的存在、位置和转录水平与角质形成细胞的可用数据进行比较,我们表明两条细胞系中相同基因的相同启动子序列具有不同的 G4 折叠状态:高转录水平始终与 G4 折叠相关。AP-1 和 SP1 转录因子的结合位点在 G4 折叠序列中最显著,它们与 G4 折叠的启动子共免疫沉淀。因此,G4 及其相关转录因子合作来确定细胞特异性转录程序,使 G4 成为转录机制的新型表观遗传调节剂。