The human RNA-DNA interactome is cell type-specific and dynamic
Year: 2026
Type: preprint
Abstract: More than twenty years ago, the FANTOM consortium uncovered that mammalian genomes are pervasively transcribed, revealing multitudes of RNAs with unknown functions. A subset of these transcripts has since then been linked to transcriptional control and to chromatin organization via their ability to interact with DNA, suggesting that chromatin-associated RNAs could be key players in genome regulation. Although recent technological advances now enable the mapping of genome-wide RNA-DNA contacts, a lack of analyses integrating these methods with other genomic features and across multiple cellular contexts hinders our comprehensive understanding of the principles underlying RNA-DNA interactions and of their biological importance. As part of the FANTOM6 project, we thus generated RNA-DNA interaction maps in 16 different human cell types, then combined these contacts with multiple layers of other genomic data to investigate how patterns of interaction between RNA and DNA relate to chromatin organization and function. We show that the RNA-DNA interactome is highly dynamic yet reproducibly organized in cell-type specific networks, constituted of a great diversity of interactions that vary in function of their distance, the nature of their sources and the chromatin state of their targets. In particular, we detected numerous regulatory elements that exhibit marked changes in activity when differentially bound by transcripts, implying that thousands of RNA-DNA interactions can play a mechanistic role in gene expression. This regulatory function correlates with RNA-protein interactions and significantly associates with cell type-relevant and disorder-related traits. In addition to providing essential resources for future research in RNA-mediated chromatin regulation, cellular biology and human diseases, our study thus establishes the RNA-DNA interactome as a new genome regulatory layer that defines and maintains cellular identity and behavior.
Authors: Alice Lambolez, Pelin Sahlén, Wenjing Kang, Xufeng Shu, Jessica Severin, Rodrigo Pracana, Ilyes Abdelhamid, Bhavya Dhaka, Christophe Vroland, Valeria Ranzani, Benedetto Polimeni, Masaru Koido, Andrea Vandelli, Maria Mintseva, Marton Rohaly Medved, Kayoko Yasuzawa, Mitsuyoshi Murata, Diane Delobel, Wing Hin Yip, Hiromi Nishiyori-Sueki, Satoshi Takizawa, Tomoe Nobusada, Matthew Brown, Valeria Di Gioia, Yoshimi Inaba, Sachi Kato, Callum Parr, Kentaro Kaji, Tsugumi Kawashima, Tsukasa Kouno, Michihira Tagami, Kokoro Ozaki, Rebecca Vadalà, Federica Marasca, Elisabetta Cozzi, Robert Krautz, Christian Vaagensø, Tomohiro Yamazaki, Xiaoze Li Wang, Quentin Verron, Yuichi Ichikawa, Jen-Chien Chang, Matthew Valentine, Hjörleifur Einarsson, Jonathan Moody, Akira Hasegawa, Ziheng Liao, Kohei Tomizuka, Artemii Zhigulev, Marco Gaviraghi, Zekiye Altan, Stefania Policicchio, Yifan Yu, Claudia Latini, Rossana Piccioni, Chiara Medaglia, Amanda Piveta Schnepper, Laura Carpen, Eugenia Ricciardelli, Matteo Bonfanti, Roberta Bosotti, Camilla Callierotti, Giulia Maria Scotti, Yung-Li Chen, Vipin Kumar, Aslihan Karabacak, Xiangfu Zhong, Aonghus Naughton, Irene Farabella, Pauline Robbe, Nicola Pirastu, Giovanni Pascarella, Lokesh P. Tripathi, Vincenzo Lagani, Robert Lehmann, Jesper Nils Tegnér, David Gomez-Cabrero, Lorenzo Calviello, Yari Ciani, Eugenio Morelli, Ivano Legnini, Colin A. Semple, Alok Sharma, Alessandro Vitriolo, Yuki Ishikawa, Laura Broglia, Miguel Ángel Berrocal Rubio, Ilaria Nisoli, Stefania Giussani, Xiaolin Li, Ilaria Castiglioni, Matteo Jacopo Marzi, Imad Abugessaisa, Stefano Gustincich, Hideya Kawaji, Yasuhiro Murakawa, Yasushi Okazaki, Nicole Soranzo, Blagoje Soskic, Giuseppe Testa, Alberto Riva, Clelia Peano, Michiel Jan Laurens De Hoon, Oliver Harschnitz, Francesco Nicassio, Nicola Crosetto, Musa Mhlanga, Dafne Campigli Di Giammartino, Chung Chau Hon, Sören Lehmann, Robin Andersson, Noriko Saitoh, Gian Gaetano Tartaglia, Anthony Mathelier, Tetsuro Hirose, Andreas Lennartsson, Beatrice Bodega, Chikashi Terao, Rory Johnson, Remo Sanges, Christine Anne Wells, Charles-Henri Lecellier, Magda Bienko, Robert S. Young, Carlo Vittorio Cannistraci, Jay Woo Shin, Takeya Kasukawa, Chi Wai Yip, Masaki Kato, Hazuki Takahashi, Piero Carninci
Institutions: RIKEN, RIKEN Center for Integrative Medical Sciences, Science for Life Laboratory, KTH Royal Institute of Technology, Karolinska Institutet, Human Technopole, Tsinghua University, University College Dublin, Centre National de la Recherche Scientifique, Université de Montpellier, Laboratoire d'Informatique, de Robotique et de Microélectronique de Montpellier, Institut de Génétique Moléculaire de Montpellier, Istituto Nazionale Genetica Molecolare, University of Milan, The University of Tokyo, Italian Institute of Technology, Scuola Internazionale Superiore di Studi Avanzati, University of Manitoba, University of Edinburgh, Yokohama City University, Institute of Genetics and Cancer, MRC Human Genetics Unit, Broad Institute, University of Copenhagen, The University of Osaka, Japanese Foundation For Cancer Research, University of Oslo, National Institute of Biomedical Innovation, Health and Nutrition, Ilia State University, King Abdullah University of Science and Technology, Universidad Pública de Navarra (UPNA), Navarrabiomed, University of Trento, Candiolo Cancer Institute, University of Turin, Korea University, University of the South Pacific, The University of Melbourne, Radboud University Nijmegen, The University of Osaka Premium Research Institute for Human Metaverse Medicine, Tokyo Metropolitan Institute of Medical Science, Juntendo University, Wellcome Sanger Institute, European Institute of Oncology, Oslo University Hospital, Zhejiang University-University of Edinburgh Institute
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7204464823