RT Journal Article SR Electronic T1 RNA:DNA hybrids in the human genome have distinctive nucleotide characteristics, chromatin composition, and transcriptional relationships JF bioRxiv FD Cold Spring Harbor Laboratory SP 020545 DO 10.1101/020545 A1 Julie Nadel A1 Rodoniki Athanasiadou A1 Christophe Lemetre A1 N. Ari Wijetunga A1 Pilib Ó Broin A1 Hanae Sato A1 Zhengdong Zhang A1 Jeffrey Jeddeloh A1 Cristina Montagna A1 Aaron Golden A1 Cathal Seoighe A1 John M. Greally YR 2015 UL http://biorxiv.org/content/early/2015/11/16/020545.abstract AB 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 indicate heterogeneous functions of these genomic elements and new insights into their formation and stability in vivo.