A comparative analysis of chromatin accessibility in cattle, pig, and mouse tissues
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RESEARCH ARTICLE
Open Access
A comparative analysis of chromatin accessibility in cattle, pig, and mouse tissues Michelle M. Halstead1, Colin Kern1, Perot Saelao1, Ying Wang1, Ganrea Chanthavixay1, Juan F. Medrano1, Alison L. Van Eenennaam1, Ian Korf1, Christopher K. Tuggle2, Catherine W. Ernst3, Huaijun Zhou1* and Pablo J. Ross1*
Abstract Background: Although considerable progress has been made towards annotating the noncoding portion of the human and mouse genomes, regulatory elements in other species, such as livestock, remain poorly characterized. This lack of functional annotation poses a substantial roadblock to agricultural research and diminishes the value of these species as model organisms. As active regulatory elements are typically characterized by chromatin accessibility, we implemented the Assay for Transposase Accessible Chromatin (ATAC-seq) to annotate and characterize regulatory elements in pigs and cattle, given a set of eight adult tissues. Results: Overall, 306,304 and 273,594 active regulatory elements were identified in pig and cattle, respectively. 71, 478 porcine and 47,454 bovine regulatory elements were highly tissue-specific and were correspondingly enriched for binding motifs of known tissue-specific transcription factors. However, in every tissue the most prevalent accessible motif corresponded to the insulator CTCF, suggesting pervasive involvement in 3-D chromatin organization. Taking advantage of a similar dataset in mouse, open chromatin in pig, cattle, and mice were compared, revealing that the conservation of regulatory elements, in terms of sequence identity and accessibility, was consistent with evolutionary distance; whereas pig and cattle shared about 20% of accessible sites, mice and ungulates only had about 10% of accessible sites in common. Furthermore, conservation of accessibility was more prevalent at promoters than at intergenic regions. Conclusions: The lack of conserved accessibility at distal elements is consistent with rapid evolution of enhancers, and further emphasizes the need to annotate regulatory elements in individual species, rather than inferring elements based on homology. This atlas of chromatin accessibility in cattle and pig constitutes a substantial step towards annotating livestock genomes and dissecting the regulatory link between genome and phenome. Keywords: Chromatin accessibility , Functional annotation , Cattle , Pig , Comparative epigenomics
* Correspondence: [email protected]; [email protected] 1 Department of Animal Science, University of California Davis, Davis, CA 95616, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or oth
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