Toward predictive R-loop computational biology: genome-scale prediction of R-loops reveals their association with complex promoter structures, G-quadruplexes and transcriptionally active enhancers

Toward predictive R-loop computational biology: genome-scale prediction of R-loops reveals their association with complex promoter structures, G-quadruplexes and transcriptionally active enhancers
Title:
Toward predictive R-loop computational biology: genome-scale prediction of R-loops reveals their association with complex promoter structures, G-quadruplexes and transcriptionally active enhancers
Other Titles:
Nucleic Acids Research
Keywords:
Publication Date:
24 July 2018
Citation:
Vladimir A Kuznetsov, Vladyslav Bondarenko, Thidathip Wongsurawat, Surya P Yenamandra, Piroon Jenjaroenpun, Toward predictive R-loop computational biology: genome-scale prediction of R-loops reveals their association with complex promoter structures, G-quadruplexes and transcriptionally active enhancers, Nucleic Acids Research, Volume 46, Issue 15, 6 September 2018, Page 8023, https://doi.org/10.1093/nar/gky690
Abstract:
R-loops are three-stranded RNA:DNA hybrid structures essential for many normal and pathobiological processes. Previously, we generated a quantitative R-loop forming sequence (RLFS) model, quantitative model of R-loop-forming sequences (QmRLFS) and predicted ∼660 000 RLFSs; most of them located in genes and gene-flanking regions, G-rich regions and disease-associated genomic loci in the human genome. Here, we conducted a comprehensive comparative analysis of these RLFSs using experimental data and demonstrated the high performance of QmRLFS predictions on the nucleotide and genome scales. The preferential co-localization of RLFS with promoters, U1 splice sites, gene ends, enhancers and non-B DNA structures, such as G-quadruplexes, provides evidence for the mechanical linkage between DNA tertiary structures, transcription initiation and R-loops in critical regulatory genome regions. We introduced and characterized an abundant class of reverse-forward RLFS clusters highly enriched in non-B DNA structures, which localized to promoters, gene ends and enhancers. The RLFS co-localization with promoters and transcriptionally active enhancers suggested new models for in cis and in trans regulation by RNA:DNA hybrids of transcription initiation and formation of 3D-chromatin loops. Overall, this study provides a rationale for the discovery and characterization of the non-B DNA regulatory structures involved in the formation of the RNA:DNA interactome as the basis for an emerging quantitative R-loop biology and pathobiology.
License type:
http://creativecommons.org/licenses/by-nc/4.0/
Funding Info:
Description:
ISSN:
0305-1048
1362-4962
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