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

Grapotte, Mathys and Saraswat, Manu and Bessière, Chloé and Menichelli, Christophe and Ramilowski, Jordan A. and Severin, Jessica and Hayashizaki, Yoshihide and Itoh, Masayoshi and Tagami, Michihira and Murata, Mitsuyoshi and Kojima-Ishiyama, Miki and Noma, Shohei and Noguchi, Shuhei and Kasukawa, Takeya and Hasegawa, Akira and Suzuki, Harukazu and Nishiyori-Sueki, Hiromi and Frith, Martin C. and Fantom consortium, and Chatelain, Clément and Carninci, Piero and de Hoon, Michiel J. L. and Wasserman, Wyeth W. and Bréhélin, Laurent and Lecellier, Charles-Henri. (2021) Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network. Nature Communications, 12 (1). p. 3297.

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Official URL: https://edoc.unibas.ch/83438/

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (van Nimwegen)
UniBasel Contributors:van Nimwegen, Erik
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:11 Feb 2022 18:45
Deposited On:31 Aug 2021 12:24

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