Multiple G-quadruplex binding ligand induced transcriptomic map of cancer cell lines

Journal of Cell Communication and Signaling - Tập 16 - Trang 129-135 - 2021
Amjesh Revikumar1, Vivek Kashyap2, Akhina Palollathil2, Anjana Aravind2, Rajeswari Raguraman1,3, Kenkere Mallikarjunaiah Kiran Kumar4, Manavalan Vijayakumar4, Thottethodi Subrahmanya Keshava Prasad2, Rajesh Raju1,2
1Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India
2Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to Be University), Mangalore, India
3Health Science Centre, University of Oklahoma, Oklahoma City, USA
4Department of Surgical Oncology, Yenepoya Medical College, Yenepoya (Deemed to be University), Mangalore, India

Tóm tắt

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.

Tài liệu tham khảo

Gellert M, Lipsett MN, Davies DR (1962) Helix formation by guanylic acid. Proc Natl Acad Sci USA 48:2013–2018

Varizhuk A, Isaakova E, Pozmogova G (2019) DNA G-quadruplexes (G4s) modulate epigenetic (Re)programming and chromatin remodeling: transient genomic G4s assist in the establishment and maintenance of epigenetic marks, while persistent G4s may erase epigenetic marks. BioEssays 41(9):e1900091