ATAC-Seq identifies regions of open chromatin in the bronchial lymph nodes of dairy calves experimentally challenged with bovine respiratory syncytial virus
Date
2021-01-06
Journal Title
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Publisher
BMC (Springer nature)
Abstract
Background: Bovine Respiratory Syncytial Virus (BRSV) is a cause of Bovine Respiratory Disease (BRD). DNA-based
biomarkers contributing to BRD resistance are potentially present in non-protein-coding regulatory regions of the
genome, which can be determined using ATAC-Seq. The objectives of this study were to: (i) identify regions of
open chromatin in DNA extracted from bronchial lymph nodes (BLN) of healthy dairy calves experimentally
challenged with BRSV and compare them with those from non-challenged healthy control calves, (ii) elucidate the
chromatin regions that were differentially or uniquely open in the BRSV challenged relative to control calves, and
(iii) compare the genes found in regions proximal to the differentially open regions to the genes previously found
to be differentially expressed in the BLN in response to BRSV and to previously identified BRD susceptibility loci.
This was achieved by challenging clinically healthy Holstein-Friesian calves (mean age 143 ± 14 days) with either
BRSV inoculum (n = 12) or with sterile phosphate buffered saline (PBS) (n = 6) and preparing and sequencing ATACSeq
libraries from fresh BLN tissues.
Results: Using Diffbind, 9,144 and 5,096 differentially accessible regions (P < 0.05, FDR < 0.05) were identified
between BRSV challenged and control calves employing DeSeq2 and EdgeR, respectively. Additionally, 8,791
chromatin regions were found to be uniquely open in BRSV challenged calves. Seventy-six and 150 of the genes
that were previously found to be differentially expressed using RNA-Seq, were located within 2 kb downstream of
the differentially accessible regions, and of the regions uniquely open in BRSV challenged calves, respectively.
Pathway analyses within ClusterProfiler indicated that these genes were involved in immune responses to infection
and participated in the Th1 and Th2 pathways, pathogen recognition and the anti-viral response. There were 237
differentially accessible regions positioned within 40 previously identified BRD susceptibility loci.
Conclusions: The identified open chromatin regions are likely to be involved in the regulatory response of gene
transcription induced by infection with BRSV. Consequently, they may contain variants which impact resistance to
BRD that could be used in breeding programmes to select healthier, more robust cattle.
Description
Publication history: Accepted - 23 November 2020; Published online - 6 January 2021.
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Article
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Keywords
ATAC-Seq, BRSV, Bovine respiratory disease, Dairy calves, Open chromatin, Gene regulation
Citation
Johnston, D., Kim, J., Taylor, J. F., Earley, B., McCabe, M. S., Lemon, K., Duffy, C., McMenamy, M., Cosby, S. L. and Waters, S. M. (2021) ‘ATAC-Seq identifies regions of open chromatin in the bronchial lymph nodes of dairy calves experimentally challenged with bovine respiratory syncytial virus’, BMC Genomics. Springer Science and Business Media LLC, 22(1). doi: 10.1186/s12864-020-07268-5.