Genetic variation in histone modifications and gene expression identifies regulatory variants in the mammary gland of cattle
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Date
2022-12-08
Open Access Location
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central Ltd
Rights
© Crown 2022
CC BY 4.0
CC BY 4.0
Abstract
BACKGROUND: Causal variants for complex traits, such as eQTL are often found in non-coding regions of the genome, where they are hypothesised to influence phenotypes by regulating gene expression. Many regulatory regions are marked by histone modifications, which can be assayed by chromatin immunoprecipitation followed by sequencing (ChIP-seq). Sequence reads from ChIP-seq form peaks at putative regulatory regions, which may reflect the amount of regulatory activity at this region. Therefore, eQTL which are also associated with differences in histone modifications are excellent candidate causal variants. RESULTS: We assayed the histone modifications H3K4Me3, H3K4Me1 and H3K27ac and mRNA in the mammary gland of up to 400 animals. We identified QTL for peak height (histone QTL), exon expression (eeQTL), allele specific expression (aseQTL) and allele specific binding (asbQTL). By intersecting these results, we identify variants which may influence gene expression by altering regulatory regions of the genome, and may be causal variants for other traits. Lastly, we find that these variants are found in putative transcription factor binding sites, identifying a mechanism for the effect of many eQTL. CONCLUSIONS: We find that allele specific and traditional QTL analysis often identify the same genetic variants and provide evidence that many eQTL are regulatory variants which alter activity at regulatory regions of the bovine genome. Our work provides methodological and biological updates on how regulatory mechanisms interplay at multi-omics levels.
Description
Keywords
ChIP-seq, allele specific QTL, bovine, causal variants, function, histone modifications, molecular QTL, regulatory variants, Cattle, Animals, Histone Code, Multiomics, Genetic Variation, Gene Expression
Citation
Prowse-Wilkins CP, Lopdell TJ, Xiang R, Vander Jagt CJ, Littlejohn MD, Chamberlain AJ, Goddard ME. (2022). Genetic variation in histone modifications and gene expression identifies regulatory variants in the mammary gland of cattle.. BMC Genomics. 23. 1. (pp. 815-).