An organism-wide ATAC-seq peak catalogue for the bovine and its use to identify regulatory variants
- Can Yuan1,
- Lijing Tang1,
- Thomas Lopdell2,
- Vyacheslav A Petrov1,
- Claire Oget-Ebrad1,
- Gabriel Costa Monteiro Moreira1,
- José Luis Gualdrón Duarte1,
- Arnaud Sartelet1,
- Zhangrui Cheng3,
- Mazdak Salavati3,
- Claire D Wathes3,
- Mark A Crowe4,
- GplusE Consortium5,
- Wouter Coppieters1,
- Mathew Littlejohn2,
- Carole Charlier1,
- Tom Druet1,
- Michel Georges1,6 and
- Haruko Takeda1
Abstract
We herein report the generation of an organism-wide catalogue 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. Correlations between the genome-wide density of peaks and transcription start sites, between peak accessibility and expression of neighboring genes, and enrichment in transcription factor binding motifs supports their regulatory potential. Using a previously established catalogue 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 due to an ~ 1.3-fold higher mutation rate within than outside peaks. Their site frequency spectrum indicates that variants in ATAC-seq peaks are subject to purifying selection. We generate eQTL datasets 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 1 in 3, and that the proportion of variants mapping to ATAC-seq peaks that are regulatory is approximately 1 in 25. We discuss the implication of these findings on the utility of ATAC-seq information to improve the accuracy of genomic selection.
- Received April 1, 2023.
- Accepted September 19, 2023.
- Published by Cold Spring Harbor Laboratory Press
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