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

   

Authors:	Grapotte, M.; Saraswat, M.; Bessière, C.; Menichelli, C.; Ramilowski, J. A.; Severin, J.; Hayashizaki, Y.; Itoh, M.; Tagami, M.; Murata, M.; Kojima-Ishiyama, M.; Noma, S.; Noguchi, S.; Kasukawa, T.; Hasegawa, A.; Suzuki, H.; Nishiyori-Sueki, H.; Frith, M. C.; FANTOM Consortium; Chatelain, C.; Carninci, P.; de Hoon, M. J. L.; Wasserman, W. W.; Bréhélin, L.; Lecellier, C. H.
Contributor:	Zabierowski, S. E.
Article Title:	Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network
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. © 2021, The Author(s).
Keywords:	promoter region; genetics; genetic analysis; mouse; animal; metabolism; animals; mice; gene expression; biology; computational biology; transcription initiation; genetic variation; microsatellite dna; dna; promoter regions, genetic; human genome; nucleotide sequence; base sequence; polymorphism, genetic; genetic marker; degenerative disease; genome, human; genetic polymorphism; microsatellite repeats; transcription initiation site; artificial neural network; neurodegenerative diseases; enhancer region; enhancer elements, genetic; probe; procedures; high throughput sequencing; high-throughput nucleotide sequencing; humans; human; a549 cells; deep learning; trapping; a-549 cell line; neural networks, computer; transcription initiation, genetic
Journal Title:	Nature Communications
Volume:	12
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2021-06-02
Start Page:	3297
Language:	English
DOI:	10.1038/s41467-021-23143-7
PUBMED:	34078885
PROVIDER:	scopus
PMCID:	PMC8172540
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85107388625&doi=10.1038%2fs41467-021-23143-7&partnerID=40&md5=507e67ac2357cc132db4d94c4fbaece3
Notes:	Article -- Erratum issued, see DOI: 10.1038/s41467-022-28758-y -- Export Date: 1 July 2021 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/182401