This article is part of the supplement: Proceedings of the Tenth Annual MCBIOS Conference
Systematic classification of non-coding RNAs by epigenomic similarity
1 Oklahoma Medical Research Foundation, Oklahoma City, Arthritis and Clinical Immunology Research Program, 825 N.E. St, Oklahoma City, OK 73104-5005, USA
2 University of Oklahoma Health Sciences Center, Department of Biochemistry and Molecular Biology, 940 Stanton L. Young Blvd, OK 73104-5005, USA
BMC Bioinformatics 2013, 14(Suppl 14):S2 doi:10.1186/1471-2105-14-S14-S2Published: 9 October 2013
Even though only 1.5% of the human genome is translated into proteins, recent reports indicate that most of it is transcribed into non-coding RNAs (ncRNAs), which are becoming the subject of increased scientific interest. We hypothesized that examining how different classes of ncRNAs co-localized with annotated epigenomic elements could help understand the functions, regulatory mechanisms, and relationships among ncRNA families.
We examined 15 different ncRNA classes for statistically significant genomic co-localizations with cell type-specific chromatin segmentation states, transcription factor binding sites (TFBSs), and histone modification marks using GenomeRunner (http://www.genomerunner.org webcite). P-values were obtained using a Chi-square test and corrected for multiple testing using the Benjamini-Hochberg procedure. We clustered and visualized the ncRNA classes by the strength of their statistical enrichments and depletions.
We found piwi-interacting RNAs (piRNAs) to be depleted in regions containing activating histone modification marks, such as H3K4 mono-, di- and trimethylation, H3K27 acetylation, as well as certain TFBSs. piRNAs were further depleted in active promoters, weak transcription, and transcription elongation regions, and enriched in repressed and heterochromatic regions. Conversely, transfer RNAs (tRNAs) were depleted in heterochromatin regions and strongly enriched in regions containing activating H3K4 di- and trimethylation marks, H2az histone variant, and a variety of TFBSs. Interestingly, regions containing CTCF insulator protein binding sites were associated with tRNAs. tRNAs were also enriched in the active, weak and poised promoters and, surprisingly, in regions with repetitive/copy number variations.
Searching for statistically significant associations between ncRNA classes and epigenomic elements permits detection of potential functional and/or regulatory relationships among ncRNA classes, and suggests cell type-specific biological roles of ncRNAs.