The human RNA-DNA interactome is cell type-specific and dynamic
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.
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BibTeX
@misc{lambolez2026human,
title = {{The human RNA-DNA interactome is cell type-specific and dynamic}},
author = {Alice Lambolez and Pelin Sahlén and Wenjing Kang and Xufeng Shu and Jessica Severin and Rodrigo Pracana and Ilyes Abdelhamid and Bhavya Dhaka and Christophe Vroland and Valeria Ranzani and Benedetto Polimeni and Masaru Koido and Andrea Vandelli and Maria Mintseva and Marton Rohaly Medved and Kayoko Yasuzawa and Mitsuyoshi Murata and Diane Delobel and Wing Hin Yip and Hiromi Nishiyori-Sueki and Satoshi Takizawa and Tomoe Nobusada and Matthew Brown and Valeria Di Gioia and Yoshimi Inaba and Sachi Kato and Callum Parr and Kentaro Kaji and Tsugumi Kawashima and Tsukasa Kouno and Michihira Tagami and Kokoro Ozaki and Rebecca Vadalà and Federica Marasca and Elisabetta Cozzi and Robert Krautz and Christian Vaagensø and Tomohiro Yamazaki and Xiaoze Li Wang and Quentin Verron and Yuichi Ichikawa and Jen-Chien Chang and Matthew Valentine and Hjörleifur Einarsson and Jonathan Moody and Akira Hasegawa and Ziheng Liao and Kohei Tomizuka and Artemii Zhigulev and Marco Gaviraghi and Zekiye Altan and Stefania Policicchio and Yifan Yu and Claudia Latini and Rossana Piccioni and Chiara Medaglia and Amanda Piveta Schnepper and Laura Carpen and Eugenia Ricciardelli and Matteo Bonfanti},
howpublished = {HAL},
year = {2026},
month = aug,
doi = {10.64898/2026.08.25.746868},
url = {https://hal.science/hal-05843238v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - UNPB
TI - The human RNA-DNA interactome is cell type-specific and dynamic
AU - Alice Lambolez
AU - Pelin Sahlén
AU - Wenjing Kang
AU - Xufeng Shu
AU - Jessica Severin
AU - Rodrigo Pracana
AU - Ilyes Abdelhamid
AU - Bhavya Dhaka
AU - Christophe Vroland
AU - Valeria Ranzani
AU - Benedetto Polimeni
AU - Masaru Koido
AU - Andrea Vandelli
AU - Maria Mintseva
AU - Marton Rohaly Medved
AU - Kayoko Yasuzawa
AU - Mitsuyoshi Murata
AU - Diane Delobel
AU - Wing Hin Yip
AU - Hiromi Nishiyori-Sueki
AU - Satoshi Takizawa
AU - Tomoe Nobusada
AU - Matthew Brown
AU - Valeria Di Gioia
AU - Yoshimi Inaba
AU - Sachi Kato
AU - Callum Parr
AU - Kentaro Kaji
AU - Tsugumi Kawashima
AU - Tsukasa Kouno
AU - Michihira Tagami
AU - Kokoro Ozaki
AU - Rebecca Vadalà
AU - Federica Marasca
AU - Elisabetta Cozzi
AU - Robert Krautz
AU - Christian Vaagensø
AU - Tomohiro Yamazaki
AU - Xiaoze Li Wang
AU - Quentin Verron
AU - Yuichi Ichikawa
AU - Jen-Chien Chang
AU - Matthew Valentine
AU - Hjörleifur Einarsson
AU - Jonathan Moody
AU - Akira Hasegawa
AU - Ziheng Liao
AU - Kohei Tomizuka
AU - Artemii Zhigulev
AU - Marco Gaviraghi
AU - Zekiye Altan
AU - Stefania Policicchio
AU - Yifan Yu
AU - Claudia Latini
AU - Rossana Piccioni
AU - Chiara Medaglia
AU - Amanda Piveta Schnepper
AU - Laura Carpen
AU - Eugenia Ricciardelli
AU - Matteo Bonfanti
PY - 2026
DA - 2026/08/26
PB - HAL
DO - 10.64898/2026.08.25.746868
UR - https://hal.science/hal-05843238v1
AB - 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.
ER -