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 Res
; 46(15): 7566-7585, 2018 09 06.
Article
en En
| MEDLINE
| ID: mdl-29945198
ABSTRACT
R-loops are three-stranded RNADNA 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 â¼660 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 RNADNA 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 RNADNA interactome as the basis for an emerging quantitative R-loop biology and pathobiology.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Genoma Humano
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Elementos de Facilitación Genéticos
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Regiones Promotoras Genéticas
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Biología Computacional
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G-Cuádruplex
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2018
Tipo del documento:
Article
País de afiliación:
Singapur