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Multiple G-quadruplex binding ligand induced transcriptomic map of cancer cell lines
Journal of Cell Communication and Signaling ( IF 4.1 ) Pub Date : 2021-07-26 , DOI: 10.1007/s12079-021-00637-z
Amjesh Revikumar 1 , Vivek Kashyap 2 , Akhina Palollathil 2 , Anjana Aravind 2 , Rajeswari Raguraman 1, 3 , Kenkere Mallikarjunaiah Kiran Kumar 4 , Manavalan Vijayakumar 4 , Thottethodi Subrahmanya Keshava Prasad 2 , Rajesh Raju 1, 2
Affiliation  

The G-quadruplexes (G4s) are a class of DNA secondary structures with guanine rich DNA sequences that can fold into four stranded non-canonical structures. At the genomic level, their pivotal role is well established in DNA replication, telomerase functions, constitution of topologically associating domains, and the regulation of gene expression. Genome instability mediated by altered G4 formation and assembly has been associated with multiple disorders including cancers and neurodegenerative disorders. Multiple tools have also been developed to predict the potential G4 regions in genomes and the whole genome G4 maps are also being derived through sequencing approaches. Enrichment of G4s in the cis-regulatory elements of genes associated with tumorigenesis has accelerated the quest for identification of G4-DNA binding ligands (G4DBLs) that can selectively bind and regulate the expression of such specific genes. In this context, the analysis of G4DBL responsive transcriptome in diverse cancer cell lines is inevitable for assessment of the specificity of novel G4DBLs. Towards this, we assembled the transcripts differentially regulated by different G4DBLs and have also identified a core set of genes regulated in diverse cancer cell lines in response to 3 or more of these ligands. With the mode of action of G4DBLs towards topology shifts, folding, or disruption of G4 structure being currently visualized, we believe that this dataset will serve as a platform for assembly of G4DBL responsive transcriptome for comparative analysis of G4DBLs in multiple cancer cells based on the expression of specific cis-regulatory G4 associated genes in the future.



中文翻译:

多个 G-四链体结合配体诱导的癌细胞系转录组图谱

G-四链体 (G4s) 是一类 DNA 二级结构,具有富含鸟嘌呤的 DNA 序列,可以折叠成四个链非规范结构。在基因组水平上,它们在 DNA 复制、端粒酶功能、拓扑相关结构域的构成和基因表达的调控中已经确立了关键作用。由改变的 G4 形成和组装介导的基因组不稳定性与多种疾病有关,包括癌症和神经退行性疾病。还开发了多种工具来预测基因组中潜在的 G4 区域,并且全基因组 G4 图也正在通过测序方法获得。与肿瘤发生相关的基因的顺式调节元件中 G4 的富集加速了对 G4-DNA 结合配体 (G4DBL) 的鉴定,这些配体可以选择性地结合和调节这些特定基因的表达。在这种情况下,对不同癌细胞系中 G4DBL 反应性转录组的分析对于评估新型 G4DBL 的特异性是不可避免的。为此,我们组装了由不同 G4DBLs 差异调节的转录物,并且还确定了一组核心基因,这些基因在不同的癌细胞系中响应于 3 个或更多这些配体而受到调节。随着 G4DBLs 对 G4 结构的拓扑变化、折叠或破坏的作用模式目前可视化,

更新日期:2021-07-26
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