Rna:dna hybrids in the human genome have distinctive nucleotide characteristics, chromatin composition, and transcriptional relationships
Nadel, Julie Athanasiadou, Rodoniki Lemetre, Christophe Wijetunga, N. Ari Ó Broin, Pilib Sato, Hanae Zhang, Zhengdong Jeddeloh, Jeffrey Montagna, Cristina Golden, Aaron
Nadel, Julie
Athanasiadou, Rodoniki
Lemetre, Christophe
Wijetunga, N. Ari
Ó Broin, Pilib
Sato, Hanae
Zhang, Zhengdong
Jeddeloh, Jeffrey
Montagna, Cristina
Golden, Aaron
Repository DOI
Publication Date
2015-11-16
Keywords
rna:DNA hybrid, r-loop, chromatin, DNA methylation, transcription factor, transcription, non-coding rna, mass spectrometry, r-loop formation, class switch sequences, factor-binding sites, human ribosomal DNA, activated t-cells, chip-seq data, rna/DNA hybrids, gene-expression, stranded rna, pause sites
Type
Article
Downloads
Citation
Nadel, Julie; Athanasiadou, Rodoniki; Lemetre, Christophe; Wijetunga, N. Ari; Ó Broin, Pilib; Sato, Hanae; Zhang, Zhengdong; Jeddeloh, Jeffrey; Montagna, Cristina; Golden, Aaron; Seoighe, Cathal; Greally, John M. (2015). Rna:dna hybrids in the human genome have distinctive nucleotide characteristics, chromatin composition, and transcriptional relationships. Epigenetics & Chromatin 8 ,
Abstract
Background: RNA:DNA hybrids represent a non-canonical nucleic acid structure that has been associated with a range of human diseases and potential transcriptional regulatory functions. Mapping of RNA:DNA hybrids in human cells reveals them to have a number of characteristics that give insights into their functions. Results: We find RNA:DNA hybrids to occupy millions of base pairs in the human genome. A directional sequencing approach shows the RNA component of the RNA:DNA hybrid to be purine-rich, indicating a thermodynamic contribution to their in vivo stability. The RNA:DNA hybrids are enriched at loci with decreased DNA methylation and increased DNase hypersensitivity, and within larger domains with characteristics of heterochromatin formation, indicating potential transcriptional regulatory properties. Mass spectrometry studies of chromatin at RNA:DNA hybrids shows the presence of the ILF2 and ILF3 transcription factors, supporting a model of certain transcription factors binding preferentially to the RNA:DNA conformation. Conclusions: Overall, there is little to indicate a dependence for RNA:DNA hybrids forming co-transcriptionally, with results from the ribosomal DNA repeat unit instead supporting the intriguing model of RNA generating these structures in trans. The results of the study
Funder
Publisher
Springer Nature
Publisher DOI
10.1186/s13072-015-0040-6
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland