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Epigenetics Chromatin. 2015 Nov 16;8:46. doi: 10.1186/s13072-015-0040-6. eCollection 2015.

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

Author information

1
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461 USA.
2
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461 USA ; Department of Biology, Center for Genomics and Systems Biology, New York University, 12 Waverly Place, New York, NY 10003 USA.
3
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461 USA ; Integrated Genomics Operation, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 USA.
4
Roche-NimbleGen, Madison, WI 53711 USA.
5
School of Mathematics, Statistics and Applied Mathematics, National University of Ireland Galway, Galway, Ireland.
6
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461 USA ; Department of Genetics, Center for Epigenomics and Division of Computational Genetics, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, NY 10461 USA.

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.

KEYWORDS:

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

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