An organism-wide ATAC-seq peak catalog for the bovine and its use to identify regulatory variants

Can Yuan, Lijing Tang, Thomas Lopdell, Vyacheslav A. Petrov, Claire Oget-Ebrad, Gabriel Costa Monteiro Moreira, José Luis Gualdrón Duarte, Arnaud Sartelet, Zhangrui Cheng, Mazdak Salavati, D. Claire Wathes, Mark A. Crowe, GplusE Consortium, Wouter Coppieters, Mathew Littlejohn, Carole Charlier, Tom Druet, Michel Georges*, Haruko Takeda

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Abstract

We report the generation of an organism-wide catalog of 976,813 cis-acting regulatory elements for the bovine detected by the assay for transposase accessible chromatin using sequencing (ATAC-seq). We regroup these regulatory elements in 16 components by nonnegative matrix factorization. Correlation between the genome-wide density of peaks and transcription start sites, correlation between peak accessibility and expression of neighboring genes, and enrichment in transcription factor binding motifs support their regulatory potential. Using a previously established catalog of 12,736,643 variants, we show that the proportion of single-nucleotide polymorphisms mapping to ATAC-seq peaks is higher than expected and that this is owing to an approximately 1.3-fold higher mutation rate within peaks. Their site frequency spectrum indicates that variants in ATAC-seq peaks are subject to purifying selection. We generate eQTL data sets for liver and blood and show that variants that drive eQTL fall into liver- and blood-specific ATAC-seq peaks more often than expected by chance. We combine ATAC-seq and eQTL data to estimate that the proportion of regulatory variants mapping to ATAC-seq peaks is approximately one in three and that the proportion of variants mapping to ATAC-seq peaks that are regulatory is approximately one in 25. We discuss the implication of these findings on the utility of ATAC-seq information to improve the accuracy of genomic selection.
OriginalsprogEngelsk
TidsskriftGenome Research
Vol/bind33
Nummer10
Sider (fra-til)1848-1864
Antal sider18
ISSN1088-9051
DOI
StatusUdgivet - okt. 2023

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