RNA:DNA hybrids in the human genome have distinctive nucleotide characteristics, chromatin composition, and transcriptional relationships

Julie Nadel, Rodoniki Athanasiadou, Christophe Lemetre, N. Ari Wijetunga, Pilib Ó Broin, Hanae Sato, Zhengdong Zhang, Jeffrey Jeddeloh, Cristina Montagna, Aaron Golden, Cathal Seoighe, John M. Greally

Research output: Contribution to journalArticle

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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 indicate heterogeneous functions of these genomic elements and new insights into their formation and stability in vivo.

Original languageEnglish (US)
Article number40
JournalEpigenetics and Chromatin
Volume8
Issue number1
DOIs
StatePublished - Nov 16 2015

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Keywords

  • Chromatin
  • DNA methylation
  • Mass spectrometry
  • Non-coding RNA
  • R-loop
  • RNA:DNA hybrid
  • Transcription
  • Transcription factor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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