Nadel Julie, Athanasiadou Rodoniki, Lemetre Christophe, Wijetunga N Ari, Ó Broin Pilib, Sato Hanae, Zhang Zhengdong, Jeddeloh Jeffrey, Montagna Cristina, Golden Aaron, Seoighe Cathal, Greally John M
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461 USA.
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.
Epigenetics Chromatin. 2015 Nov 16;8:46. doi: 10.1186/s13072-015-0040-6. eCollection 2015.
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.
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.
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.
RNA:DNA杂交体代表一种非经典核酸结构,与一系列人类疾病及潜在转录调控功能相关。对人类细胞中RNA:DNA杂交体的定位揭示了它们具有一些有助于深入了解其功能的特征。
我们发现RNA:DNA杂交体在人类基因组中占据数百万碱基对。一种定向测序方法显示,RNA:DNA杂交体的RNA成分富含嘌呤,这表明其对体内稳定性有热力学贡献。RNA:DNA杂交体在DNA甲基化降低和DNase超敏性增加的位点富集,且在具有异染色质形成特征的较大区域内富集,这表明其具有潜在的转录调控特性。对RNA:DNA杂交体处染色质的质谱研究表明存在ILF2和ILF3转录因子,支持了某些转录因子优先结合RNA:DNA构象的模型。
总体而言,几乎没有迹象表明RNA:DNA杂交体依赖于共转录形成,核糖体DNA重复单元的结果反而支持了RNA在反式作用中产生这些结构的有趣模型。该研究结果表明了这些基因组元件的异质功能以及对其在体内形成和稳定性的新见解。