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

TY - JOUR

T1 - An organism-wide ATAC-seq peak catalog for the bovine and its use to identify regulatory variants

AU - Yuan, Can

AU - Tang, Lijing

AU - Lopdell, Thomas

AU - Petrov, Vyacheslav A.

AU - Oget-Ebrad, Claire

AU - Moreira, Gabriel Costa Monteiro

AU - Duarte, José Luis Gualdrón

AU - Sartelet, Arnaud

AU - Cheng, Zhangrui

AU - Salavati, Mazdak

AU - Wathes, D. Claire

AU - Crowe, Mark A.

AU - GplusE Consortium

AU - Coppieters, Wouter

AU - Littlejohn, Mathew

AU - Charlier, Carole

AU - Druet, Tom

AU - Georges, Michel

AU - Takeda, Haruko

AU - Ingvartsen, Klaus L.

AU - Foldager, Leslie

AU - Rousing, Tine

AU - Østergaard, Søren

AU - Sørensen, Martin Tang

PY - 2023/10

Y1 - 2023/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85176496042&partnerID=8YFLogxK

U2 - 10.1101/gr.277947.123

DO - 10.1101/gr.277947.123

M3 - Journal article

C2 - 37751945

SN - 1088-9051

VL - 33

SP - 1848

EP - 1864

JO - Genome Research

JF - Genome Research

IS - 10

ER -