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

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Item Type:Article
Title:Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network
Creators Name:Grapotte, M. and Saraswat, M. and Bessière, C. and Menichelli, C. and Ramilowski, J.A. and Severin, J. and Hayashizaki, Y. and Itoh, M. and Tagami, M. and Murata, M. and Kojima-Ishiyama, M. and Noma, S. and Noguchi, S. and Kasukawa, T. and Hasegawa, A. and Suzuki, H. and Nishiyori-Sueki, H. and Frith, M.C. and Chatelain, C. and Carninci, P. and de Hoon, M.J.L. and Wasserman, W.W. and Bréhélin, L. and Lecellier, C.H.
Abstract: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.
Keywords:A549 Cells, Base Sequence, Computational Biology, Computer Neural Networks, Deep Learning, Genetic Enhancer Elements, Genetic Polymorphism, Genetic Promoter Regions, Genetic Transcription Initiation, High-Throughput Nucleotide Sequencing, Human Genome, Microsatellite Repeats, Neurodegenerative Diseases, Transcription Initiation Site, Animals, Mice
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:3297
Date:2 June 2021
Additional Information:Giulia Caglio, Ana Miguel Fernandes, Carmelo Ferrai, Alexander Kukalev, Ana Pombo, Tiago Rito, Marcus Schueler and Elena Torlai Triglia are members of the FANTOM consortium. Erratum in: Nat Commun 13, 1200.
Official Publication:https://doi.org/10.1038/s41467-021-23143-7
PubMed:View item in PubMed

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