An organism-wide ATAC-seq peak catalog 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 Sartelet3,
- Zhangrui Cheng4,
- Mazdak Salavati4,8,
- D. Claire Wathes4,
- Mark A. Crowe5,
- GplusE Consortium5,7,
- Wouter Coppieters6,
- Mathew Littlejohn2,
- Carole Charlier1,
- Tom Druet1,
- Michel Georges1 and
- Haruko Takeda1
- 1Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, University of Liège, 4000 Liège, Belgium;
- 2Research and Development, Livestock Improvement Corporation, Hamilton 3240, New Zealand;
- 3Clinical Department of Ruminant, University of Liège, 4000 Liège, Belgium;
- 4Royal Veterinary College, Hatfield, Herts AL9 7TA, United Kingdom;
- 5School of Veterinary Medicine, University College Dublin, Dublin 4, Ireland;
- 6GIGA Genomics platform, GIGA Institute, University of Liège, 4000 Liège, Belgium
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.
Footnotes
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↵7 A complete list of the GplusE Consortium authors appears at the end of this paper.
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.277947.123.
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↵9 School of Veterinary Medicine, University College Dublin, Dublin 4, Ireland
- Received April 1, 2023.
- Accepted September 19, 2023.
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