Genome-wide profiling of yeast DNA:RNA hybrid prone sites with DRIP-chip

PLoS Genet. 2014 Apr 17;10(4):e1004288. doi: 10.1371/journal.pgen.1004288. eCollection 2014 Apr.


DNA:RNA hybrid formation is emerging as a significant cause of genome instability in biological systems ranging from bacteria to mammals. Here we describe the genome-wide distribution of DNA:RNA hybrid prone loci in Saccharomyces cerevisiae by DNA:RNA immunoprecipitation (DRIP) followed by hybridization on tiling microarray. These profiles show that DNA:RNA hybrids preferentially accumulated at rDNA, Ty1 and Ty2 transposons, telomeric repeat regions and a subset of open reading frames (ORFs). The latter are generally highly transcribed and have high GC content. Interestingly, significant DNA:RNA hybrid enrichment was also detected at genes associated with antisense transcripts. The expression of antisense-associated genes was also significantly altered upon overexpression of RNase H, which degrades the RNA in hybrids. Finally, we uncover mutant-specific differences in the DRIP profiles of a Sen1 helicase mutant, RNase H deletion mutant and Hpr1 THO complex mutant compared to wild type, suggesting different roles for these proteins in DNA:RNA hybrid biology. Our profiles of DNA:RNA hybrid prone loci provide a resource for understanding the properties of hybrid-forming regions in vivo, extend our knowledge of hybrid-mitigating enzymes, and contribute to models of antisense-mediated gene regulation. A summary of this paper was presented at the 26th International Conference on Yeast Genetics and Molecular Biology, August 2013.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antisense Elements (Genetics) / genetics
  • DNA Helicases / genetics
  • DNA, Fungal / genetics*
  • DNA, Ribosomal / genetics
  • Gene Expression Regulation, Fungal / genetics*
  • Genome-Wide Association Study / methods
  • Immunoprecipitation / methods
  • Nuclear Proteins / genetics
  • Nucleic Acid Hybridization / genetics*
  • Oligonucleotide Array Sequence Analysis / methods
  • Open Reading Frames / genetics
  • RNA, Fungal / genetics*
  • Recombination, Genetic / genetics
  • Retroelements / genetics
  • Ribonuclease H / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Sequence Deletion / genetics
  • Transcription, Genetic / genetics


  • Antisense Elements (Genetics)
  • DNA, Fungal
  • DNA, Ribosomal
  • HPR1 protein, S cerevisiae
  • Nuclear Proteins
  • RNA, Fungal
  • Retroelements
  • Saccharomyces cerevisiae Proteins
  • Ribonuclease H
  • DNA Helicases