Document Type

Article

Publication Date

6-2-2021

Publication Title

Nat Commun

Keywords

JMG, A549 Cells, Animals, Base Sequence, Computational Biology, Deep Learning, Enhancer Elements, Genetic, Genome, Human, High-Throughput Nucleotide Sequencing, Humans, Mice, Microsatellite Repeats, Neural Networks, Computer, Neurodegenerative Diseases, Polymorphism, Genetic, Promoter Regions, Genetic, Transcription Initiation Site, Transcription Initiation, Genetic

JAX Source

Nat Commun 2021 Jun 2; 12(1):3297

Volume

12

Issue

1

First Page

3297

Last Page

3297

ISSN

2041-1723

PMID

34078885

DOI

https://doi.org/10.1038/s41467-021-23143-7

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.

Comments

This article is licensed under a Creative Commons Attribution 4.0 International License.

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