Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network
Authors: Grapotte Mathys , Saraswat Manu , Bessière Chloé , Menichelli Christophe , Ramilowski Jordan A. , Severin Jessica , Hayashizaki Yoshihide , Itoh Masayoshi , Tagami Michihira , Murata Mitsuyoshi , Kojima-Ishiyama Miki , Noma Shohei , Noguchi Shuhei , Kasukawa Takeya , Hasegawa Akira , Suzuki Harukazu , Nishiyori-Sueki Hiromi , Frith Martin C. ,   FANTOM consortium, Abugessaisa Imad , Aitken Stuart , Aken Bronwen L. , Alam Intikhab , Alam Tanvir , Alasiri Rami , Alhendi Ahmad M. N. , Alinejad-Rokny Hamid , Alvarez Mariano J. , Andersson Robin , Arakawa Takahiro , Araki Marito , Arbel Taly , Archer John , Archibald Alan L. , Arner Erik , Arner Peter , Asai Kiyoshi , Ashoor Haitham , Astrom Gaby , Babina Magda , Baillie J. Kenneth , Bajic Vladimir B. , Bajpai Archana , Baker Sarah , Baldarelli Richard M. , Balic Adam , Bansal Mukesh , Batagov Arsen O. , Batzoglou Serafim , Beckhouse Anthony G. , Beltrami Antonio P. , Beltrami Carlo A. , Bertin Nicolas , Bhattacharya Sharmodeep , Bickel Peter J. , Blake Judith A. , Blanchette Mathieu , Bodega Beatrice , Bonetti Alessandro , Bono Hidemasa , Bornholdt Jette , Bttcher Michael , Bougouffa Salim , Boyd Mette , Breda Jeremie , Brombacher Frank , Brown James B. , Bult Carol J. , Burroughs A. Maxwell , Burt Dave W. , Busch Annika , Caglio Giulia , Califano Andrea , Cameron Christopher J. , Cannistraci Carlo V. , Carbone Alessandra , Carlisle Ailsa J. , Carninci Piero , Carter Kim W. , Cesselli Daniela , Chang Jen-Chien , Chen Julie C. , Chen Yun , Chierici Marco , Christodoulou John , Ciani Yari , Clark Emily L. , Coskun Mehmet , Dalby Maria , Dalla Emiliano , Daub Carsten O. , Davis Carrie A. , de Hoon Michiel J. L. , de Rie Derek , Denisenko Elena , Deplancke Bart , Detmar Michael , Deviatiiarov Ruslan , Di Bernardo Diego , Diehl Alexander D. , Dieterich Lothar C. , Dimont Emmanuel , Djebali Sarah , Dohi Taeko , Dostie Jose , Drablos Finn , Edge Albert S. B. , Edinger Matthias , Ehrlund Anna , Ekwall Karl , Elofsson Arne , Endoh Mitsuhiro , Enomoto Hideki , Enomoto Saaya , Faghihi Mohammad , Fagiolini Michela , Farach-Carson Mary C. , Faulkner Geoffrey J. , Favorov Alexander , Fernandes Ana Miguel , Ferrai Carmelo , Forrest Alistair R. R. , Forrester Lesley M. , Forsberg Mattias , Fort Alexandre , Francescatto Margherita , Freeman Tom C. , Frith Martin , Fukuda Shinji , Funayama Manabu , Furlanello Cesare , Furuno Masaaki , Furusawa Chikara , Gao Hui , Gazova Iveta , Gebhard Claudia , Geier Florian , Geijtenbeek Teunis B. H. , Ghosh Samik , Ghosheh Yanal , Gingeras Thomas R. , Gojobori Takashi , Goldberg Tatyana , Goldowitz Daniel , Gough Julian , Greco Dario , Gruber Andreas J. , Guhl Sven , Guigo Roderic , Guler Reto , Gusev Oleg , Gustincich Stefano , Ha Thomas J. , Haberle Vanja , Hale Paul , Hallstrom Bjrn M. , Hamada Michiaki , Handoko Lusy , Hara Mitsuko , Harbers Matthias , Harrow Jennifer , Harshbarger Jayson , Hase Takeshi , Hasegawa Akira , Hashimoto Kosuke , Hatano Taku , Hattori Nobutaka , Hayashi Ryuhei , Hayashizaki Yoshihide , Herlyn Meenhard , Heutink Peter , Hide Winston , Hitchens Kelly J. , Sui Shannon Ho , ’t Hoen Peter A. C. , Hon Chung Chau , Hori Fumi , Horie Masafumi , Horimoto Katsuhisa , Horton Paul , Hou Rui , Huang Edward , Huang Yi , Hugues Richard , Hume David , Ienasescu Hans , Iida Kei , Ikawa Tomokatsu , Ikemura Toshimichi , Ikeo Kazuho , Inoue Norihiko , Ishizu Yuri , Ito Yosuke , Itoh Masayoshi , Ivshina Anna V. , Jankovic Boris R. , Jenjaroenpun Piroon , Johnson Rory , Jorgensen Mette , Jorjani Hadi , Joshi Anagha , Jurman Giuseppe , Kaczkowski Bogumil , Kai Chieko , Kaida Kaoru , Kajiyama Kazuhiro , Kaliyaperumal Rajaram , Kaminuma Eli , Kanaya Takashi , Kaneda Hiroshi , Kapranov Philip , Kasianov Artem S. , Kasukawa Takeya , Katayama Toshiaki , Kato Sachi , Kawaguchi Shuji , Kawai Jun , Kawaji Hideya , Kawamoto Hiroshi , Kawamura Yuki I. , Kawasaki Satoshi , Kawashima Tsugumi , Kempfle Judith S. , Kenna Tony J. , Kere Juha , Khachigian Levon , Kiryu Hisanori , Kishima Mami , Kitajima Hiroyuki , Kitamura Toshio , Kitano Hiroaki , Klaric Enio , Klepper Kjetil , Klinken S. Peter , Kloppmann Edda , Knox Alan J. , Kodama Yuichi , Kogo Yasushi , Kojima Miki , Kojima Soichi , Komatsu Norio , Komiyama Hiromitsu , Kono Tsukasa , Koseki Haruhiko , Koyasu Shigeo , Kratz Anton , Kukalev Alexander , Kulakovskiy Ivan , Kundaje Anshul , Kunikata Hiroshi , Kuo Richard , Kuo Tony , Kuraku Shigehiro , Kuznetsov Vladimir A. , Kwon Tae Jun , Larouche Matt , Lassmann Timo , Law Andy , Le-Cao Kim-Anh , Lecellier Charles-Henri , Lee Weonju , Lenhard Boris , Lennartsson Andreas , Li Kang , Li Ruohan , Lilje Berit , Lipovich Leonard , Lizio Marina , Lopez Gonzalo , Magi Shigeyuki , Mak Gloria K. , Makeev Vsevolod , Manabe Riichiro , Mandai Michiko , Mar Jessica , Maruyama Kazuichi , Maruyama Taeko , Mason Elizabeth , Mathelier Anthony , Matsuda Hideo , Medvedeva Yulia A. , Meehan Terrence F. , Mejhert Niklas , Meynert Alison , Mikami Norihisa , Minoda Akiko , Miura Hisashi , Miyagi Yohei , Miyawaki Atsushi , Mizuno Yosuke , Morikawa Hiromasa , Morimoto Mitsuru , Morioka Masaki , Morishita Soji , Moro Kazuyo , Motakis Efthymios , Motohashi Hozumi , Mukarram Abdul Kadir , Mummery Christine L. , Mungall Christopher J. , Murakawa Yasuhiro , Muramatsu Masami , Murata Mitsuyoshi , Nagasaka Kazunori , Nagase Takahide , Nakachi Yutaka , Nakahara Fumio , Nakai Kenta , Nakamura Kumi , Nakamura Yasukazu , Nakamura Yukio , Nakazawa Toru , Nason Guy P. , Nepal Chirag , Nguyen Quan Hoang , Nielsen Lars K. , Nishida Kohji , Nishiguchi Koji M. , Nishiyori Hiromi , Nitta Kazuhiro , Noguchi Shuhei , Noma Shohei , Notredame Cedric , Ogishima Soichi , Ohkura Naganari , Ohno Hiroshi , Ohshima Mitsuhiro , Ohtsu Takashi , Okada Yukinori , Okada-Hatakeyama Mariko , Okazaki Yasushi , Oksvold Per , Orlando Valerio , Ow Ghim Sion , Ozturk Mumin , Pachkov Mikhail , Paparountas Triantafyllos , Parihar Suraj P. , Park Sung-Joon , Pascarella Giovanni , Passier Robert , Persson Helena , Philippens Ingrid H. , Piazza Silvano , Plessy Charles , Pombo Ana , Ponten Fredrik , Poulain Stéphane , Poulsen Thomas M. , Pradhan Swati , Prezioso Carolina , Pridans Clare , Qin Xiang-Yang , Quackenbush John , Rackham Owen , Ramilowski Jordan , Ravasi Timothy , Rehli Michael , Rennie Sarah , Rito Tiago , Rizzu Patrizia , Robert Christelle , Roos Marco , Rost Burkhard , Roudnicky Filip , Roy Riti , Rye Morten B. , Sachenkova Oxana , Saetrom Pal , Sai Hyonmi , Saiki Shinji , Saito Mitsue , Saito Akira , Sakaguchi Shimon , Sakai Mizuho , Sakaue Saori , Sakaue-Sawano Asako , Sandelin Albin , Sano Hiromi , Sasamoto Yuzuru , Sato Hiroki , Saxena Alka , Saya Hideyuki , Schafferhans Andrea , Schmeier Sebastian , Schmidl Christian , Schmocker Daniel , Schneider Claudio , Schueler Marcus , Schultes Erik A. , Schulze-Tanzil Gundula , Semple Colin A. , Seno Shigeto , Seo Wooseok , Sese Jun , Severin Jessica , Sheng Guojun , Shi Jiantao , Shimoni Yishai , Shin Jay W. , SimonSanchez Javier , Sivertsson Asa , Sjostedt Evelina , Soderhall Cilla , Laurent Georges St , Stoiber Marcus H. , Sugiyama Daisuke , Summers Kim M. , Suzuki Ana Maria , Suzuki Harukazu , Suzuki Kenji , Suzuki Mikiko , Suzuki Naoko , Suzuki Takahiro , Swanson Douglas J. , Swoboda Rolf K. , Tagami Michihira , Taguchi Ayumi , Takahashi Hazuki , Takahashi Masayo , Takamochi Kazuya , Takeda Satoru , Takenaka Yoichi , Tam Kin Tung , Tanaka Hiroshi , Tanaka Rica , Tanaka Yuji , Tang Dave , Taniuchi Ichiro , Tanzer Andrea , Tarui Hiroshi , Taylor Martin S. , Terada Aika , Terao Yasuhisa , Testa Alison C. , Thomas Mark , Thongjuea Supat , Tomii Kentaro , Torlai Triglia Elena , Toyoda Hiroo , Tsang H. Gwen , Tsujikawa Motokazu , Uhlén Mathias , Valen Eivind , van de Wetering Marc , van Nimwegen Erik , Velmeshev Dmitry , Verardo Roberto , Vitezic Morana , Vitting-Seerup Kristoffer , von Feilitzen Kalle , Voolstra Christian R. , Vorontsov Ilya E. , Wahlestedt Claes , Wasserman Wyeth W. , Watanabe Kazuhide , Watanabe Shoko , Wells Christine A. , Winteringham Louise N. , Wolvetang Ernst , Yabukami Haruka , Yagi Ken , Yamada Takuji , Yamaguchi Yoko , Yamamoto Masayuki , Yamamoto Yasutomo , Yamamoto Yumiko , Yamanaka Yasunari , Yano Kojiro , Yasuzawa Kayoko , Yatsuka Yukiko , Yo Masahiro , Yokokura Shunji , Yoneda Misako , Yoshida Emiko , Yoshida Yuki , Yoshihara Masahito , Young Rachel , Young Robert S. , Yu Nancy Y. , Yumoto Noriko , Zabierowski Susan E. , Zhang Peter G. , Zucchelli Silvia , Zwahlen Martin , Chatelain Clément , Carninci Piero , de Hoon Michiel J. L. , Wasserman Wyeth W. , Bréhélin Laurent , Lecellier Charles-Henri 
Published: June 2021

AbstractUsing 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.