RADICL-seq identifies general and cell type–specific principles of genome-wide RNA-chromatin interactions

• Published in: Nature communications Vol. 11; no. 1; pp. 1018 - 14
• Main Authors: Bonetti, Alessandro, Agostini, Federico, Suzuki, Ana Maria, Hashimoto, Kosuke, Pascarella, Giovanni, Gimenez, Juliette, Roos, Leonie, Nash, Alex J., Ghilotti, Marco, Cameron, Christopher J. F., Valentine, Matthew, Medvedeva, Yulia A., Noguchi, Shuhei, Agirre, Eneritz, Kashi, Kaori, Samudyata, Luginbühl, Joachim, Cazzoli, Riccardo, Agrawal, Saumya, Luscombe, Nicholas M., Blanchette, Mathieu, Kasukawa, Takeya, Hoon, Michiel de, Arner, Erik, Lenhard, Boris, Plessy, Charles, Castelo-Branco, Gonçalo, Orlando, Valerio, Carninci, Piero
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.02.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 38; 45; 45/23; 49/22; 49/90; 49/91; 631/1647; 631/337/100; Animals; Cell Line; Cell Nucleus - genetics; Cell Nucleus - metabolism; Chromatin - genetics; Chromatin - metabolism; Chromatin Assembly and Disassembly - genetics; Chromatin remodeling; Chromosome Mapping - methods; Deoxyribonucleic acid; DNA; Gene expression; Gene Library; Gene mapping; Genomes; Genomics; High-Throughput Nucleotide Sequencing - methods; Humanities and Social Sciences; Identification methods; Localization; Mammals; Mapping; Mice; Mouse Embryonic Stem Cells; multidisciplinary; Nuclei; Nuclei (cytology); Nucleotide sequence; Occupancy; Ribonucleic acid; RNA; RNA, Untranslated - genetics; RNA, Untranslated - metabolism; Science; Science (multidisciplinary); Sequence Analysis, RNA - methods; Transcription; Transcription, Genetic
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-14337-6

Mammalian genomes encode tens of thousands of noncoding RNAs. Most noncoding transcripts exhibit nuclear localization and several have been shown to play a role in the regulation of gene expression and chromatin remodeling. To investigate the function of such RNAs, methods to massively map the genomic interacting sites of multiple transcripts have been developed; however, these methods have some limitations. Here, we introduce RNA And DNA Interacting Complexes Ligated and sequenced (RADICL-seq), a technology that maps genome-wide RNA–chromatin interactions in intact nuclei. RADICL-seq is a proximity ligation-based methodology that reduces the bias for nascent transcription, while increasing genomic coverage and unique mapping rate efficiency compared with existing methods. RADICL-seq identifies distinct patterns of genome occupancy for different classes of transcripts as well as cell type–specific RNA-chromatin interactions, and highlights the role of transcription in the establishment of chromatin structure. Mammalian genomes encode tens of thousands of ncRNAs that have important roles in regulation of gene expression and chromatin organization. Here, the authors present RADICLseq to map RNA-chromatin interactions in intact nuclei to shed light on these fine-tuned processes.