Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Mathys Grapotte, Manu Saraswat, Chloé Bessière, Christophe Menichelli, Jordan A. Ramilowski, Jessica Severin, Yoshihide Hayashizaki, Masayoshi Itoh, Michihira Tagami, Mitsuyoshi Murata, Miki Kojima-ishiyama, Shohei Noma, Shuhei Noguchi, Takeya Kasukawa, Akira Hasegawa, Harukazu Suzuki, Hiromi Nishiyori-sueki, Martin Frith, Imad Abugessaisa, Stuart AitkenBronwen L. Aken, Intikhab Alam, Tanvir Alam, Rami Alasiri, Ahmad M. N. Alhendi, Hamid Alinejad-rokny, Mariano J. Alvarez, Robin Andersson, Takahiro Arakawa, Marito Araki, Taly Arbel, John Archer, Alan L. Archibald, Erik Arner, Peter Arner, Kiyoshi Asai, Haitham Ashoor, Gaby Astrom, Magda Babina, J. Kenneth Baillie, Vladimir B. Bajic, Archana Bajpai, Sarah Baker, Richard M. Baldarelli, Adam Balic, Mukesh Bansal, Arsen O. Batagov, Serafim Batzoglou, Anthony G. Beckhouse, Antonio P. Beltrami, Carlo A. Beltrami, Nicolas Bertin, Sharmodeep Bhattacharya, Peter J. Bickel, Judith A. Blake, Mathieu Blanchette, Beatrice Bodega, Alessandro Bonetti, Hidemasa Bono, Jette Bornholdt, Michael Bttcher, Salim Bougouffa, Mette Boyd, Jeremie Breda, Frank Brombacher, James B. Brown, Carol J. Bult, A. Maxwell Burroughs, Dave W. Burt, Annika Busch, Giulia Caglio, Andrea Califano, Christopher J. Cameron, Carlo V. Cannistraci, Alessandra Carbone, Ailsa J. Carlisle, Piero Carninci, Kim W. Carter, Daniela Cesselli, Jen-chien Chang, Julie C. Chen, Yun Chen, Marco Chierici, John Christodoulou, Yari Ciani, Emily L. Clark, Mehmet Coskun, Maria Dalby, Emiliano Dalla, Carsten O. Daub, Carrie A. Davis, Michiel J. L. De Hoon, Derek De Rie, Elena Denisenko, Bart Deplancke, Michael Detmar, Ruslan Deviatiiarov, Diego Di Bernardo, Alexander D. Diehl, Lothar C. Dieterich, Emmanuel Dimont, Sarah Djebali, Taeko Dohi, Jose Dostie, Finn Drablos, Albert S. B. 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Hallstrom, Michiaki Hamada, Lusy Handoko, Mitsuko Hara, Matthias Harbers, Jennifer Harrow, Jayson Harshbarger, Takeshi Hase, Akira Hasegawa, Kosuke Hashimoto, Taku Hatano, Nobutaka Hattori, Ryuhei Hayashi, Yoshihide Hayashizaki, Meenhard Herlyn, Kristina Hettne, Peter Heutink, Winston Hide, Kelly J. Hitchens, Shannon Ho Sui, Peter A. C. ’t Hoen, Chung Chau Hon, Fumi Hori, Masafumi Horie, Katsuhisa Horimoto, Paul Horton, Rui Hou, Edward Huang, Yi Huang, Richard Hugues, David Hume, Hans Ienasescu, Kei Iida, Tomokatsu Ikawa, Toshimichi Ikemura, Kazuho Ikeo, Norihiko Inoue, Yuri Ishizu, Yosuke Ito, Masayoshi Itoh, Anna V. Ivshina, Boris R. Jankovic, Piroon Jenjaroenpun, Rory Johnson, Mette Jorgensen, Hadi Jorjani, Anagha Joshi, Giuseppe Jurman, Bogumil Kaczkowski, Chieko Kai, Kaoru Kaida, Kazuhiro Kajiyama, Rajaram Kaliyaperumal, Eli Kaminuma, Takashi Kanaya, Hiroshi Kaneda, Philip Kapranov, Artem S. Kasianov, Takeya Kasukawa, Toshiaki Katayama, Sachi Kato, Shuji Kawaguchi, Jun Kawai, Hideya Kawaji, Hiroshi Kawamoto, Yuki I. Kawamura, Satoshi Kawasaki, Tsugumi Kawashima, Judith S. Kempfle, Tony J. Kenna, Juha Kere, Levon Khachigian, Hisanori Kiryu, Mami Kishima, Hiroyuki Kitajima, Toshio Kitamura, Hiroaki Kitano, Enio Klaric, Kjetil Klepper, S. Peter Klinken, Edda Kloppmann, Alan J. Knox, Yuichi Kodama, Yasushi Kogo, Miki Kojima, Soichi Kojima, Norio Komatsu, Hiromitsu Komiyama, Tsukasa Kono, Haruhiko Koseki, Shigeo Koyasu, Anton Kratz, Alexander Kukalev, Ivan Kulakovskiy, Anshul Kundaje, Hiroshi Kunikata, Richard Kuo, Tony Kuo, Shigehiro Kuraku, Vladimir A. Kuznetsov, Tae Jun Kwon, Matt Larouche, Timo Lassmann, Andy Law, Kim-anh Le-cao, Charles-henri Lecellier, Weonju Lee, Boris Lenhard, Andreas Lennartsson, Kang Li, Ruohan Li, Berit Lilje, Leonard Lipovich, Marina Lizio, Gonzalo Lopez, Shigeyuki Magi, Gloria K. Mak, Vsevolod Makeev, Riichiro Manabe, Michiko Mandai, Jessica Mar, Kazuichi Maruyama, Taeko Maruyama, Elizabeth Mason, Anthony Mathelier, Hideo Matsuda, Yulia A. Medvedeva, Terrence F. Meehan, Niklas Mejhert, Alison Meynert, Norihisa Mikami, Akiko Minoda, Hisashi Miura, Yohei Miyagi, Atsushi Miyawaki, Yosuke Mizuno, Hiromasa Morikawa, Mitsuru Morimoto, Masaki Morioka, Soji Morishita, Kazuyo Moro, Efthymios Motakis, Hozumi Motohashi, Abdul Kadir Mukarram, Christine L. Mummery, Christopher J. Mungall, Yasuhiro Murakawa, Masami Muramatsu, Mitsuyoshi Murata, Kazunori Nagasaka, Takahide Nagase, Yutaka Nakachi, Fumio Nakahara, Kenta Nakai, Kumi Nakamura, Yasukazu Nakamura, Yukio Nakamura, Toru Nakazawa, Guy P. Nason, Chirag Nepal, Quan Hoang Nguyen, Lars K. Nielsen, Kohji Nishida, Koji M. 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Rye, Oxana Sachenkova, Pal Saetrom, Hyonmi Sai, Shinji Saiki, Mitsue Saito, Akira Saito, Shimon Sakaguchi, Mizuho Sakai, Saori Sakaue, Asako Sakaue-sawano, Albin Sandelin, Hiromi Sano, Yuzuru Sasamoto, Hiroki Sato, Alka Saxena, Hideyuki Saya, Andrea Schafferhans, Sebastian Schmeier, Christian Schmidl, Daniel Schmocker, Claudio Schneider, Marcus Schueler, Erik A. Schultes, Gundula Schulze-tanzil, Colin A. Semple, Shigeto Seno, Wooseok Seo, Jun Sese, Jessica Severin, Guojun Sheng, Jiantao Shi, Yishai Shimoni, Jay W. Shin, Javier Simonsanchez, Asa Sivertsson, Evelina Sjostedt, Cilla Soderhall, Georges St Laurent, Marcus H. Stoiber, Daisuke Sugiyama, Kim M. Summers, Ana Maria Suzuki, Harukazu Suzuki, Kenji Suzuki, Mikiko Suzuki, Naoko Suzuki, Takahiro Suzuki, Douglas J. Swanson, Rolf K. Swoboda, Michihira Tagami, Ayumi Taguchi, Hazuki Takahashi, Masayo Takahashi, Kazuya Takamochi, Satoru Takeda, Yoichi Takenaka, Kin Tung Tam, Hiroshi Tanaka, Rica Tanaka, Yuji Tanaka, Dave Tang, Ichiro Taniuchi, Andrea Tanzer, Hiroshi Tarui, Martin S. Taylor, Aika Terada, Yasuhisa Terao, Alison C. Testa, Mark Thomas, Supat Thongjuea, Kentaro Tomii, Elena Torlai Triglia, Hiroo Toyoda, H. Gwen Tsang, Motokazu Tsujikawa, Mathias Uhlén, Eivind Valen, Marc Van De Wetering, Erik Van Nimwegen, Dmitry Velmeshev, Roberto Verardo, Morana Vitezic, Kristoffer Vitting-seerup, Kalle Von Feilitzen, Christian R. Voolstra, Ilya E. Vorontsov, Claes Wahlestedt, Wyeth W. Wasserman, Kazuhide Watanabe, Shoko Watanabe, Christine A. Wells, Louise N. Winteringham, Ernst Wolvetang, Haruka Yabukami, Ken Yagi, Takuji Yamada, Yoko Yamaguchi, Masayuki Yamamoto, Yasutomo Yamamoto, Yumiko Yamamoto, Yasunari Yamanaka, Kojiro Yano, Kayoko Yasuzawa, Yukiko Yatsuka, Masahiro Yo, Shunji Yokokura, Misako Yoneda, Emiko Yoshida, Yuki Yoshida, Masahito Yoshihara, Rachel Young, Robert S. Young, Nancy Y. Yu, Noriko Yumoto, Susan E. Zabierowski, Peter G. Zhang, Silvia Zucchelli, Martin Zwahlen, Clément Chatelain, Piero Carninci, Michiel J. L. De Hoon, Wyeth W. Wasserman, Laurent Bréhélin, Charles-henri Lecellier

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.
Original languageEnglish
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - 2 Jun 2021

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