Comparative whole genome DNA methylation profiling across cattle tissues reveals global and tissue-specific methylation patterns

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dc.contributor.authorZhou, Yang
dc.contributor.authorLiu, Shuli
dc.contributor.authorHu, Yan
dc.contributor.authorFang, Lingzhao
dc.contributor.authorGao, Yahui
dc.contributor.authorXia, Han
dc.contributor.authorSchroeder, Steven G.
dc.contributor.authorRosen, Benjamin D.
dc.contributor.authorConnor, Erin E.
dc.contributor.authorLi, Cong-jun
dc.contributor.authorBaldwin, Ransom L.
dc.contributor.authorCole, John B.
dc.contributor.authorVan Tassell, Curtis P.
dc.contributor.authorYang, Liguo
dc.contributor.authorMa, Li
dc.contributor.authorLiu, George E.
dc.date.accessioned2021-04-01T19:41:34Z
dc.date.available2021-04-01T19:41:34Z
dc.date.issued2020-07-06
dc.description.abstractEfforts to improve animal health, and understand genetic bases for production, may benefit from a comprehensive analysis of animal genomes and epigenomes. Although DNA methylation has been well studied in humans and other model species, its distribution patterns and regulatory impacts in cattle are still largely unknown. Here, we present the largest collection of cattle DNA methylation epigenomic data to date. Using Holstein cattle, we generated 29 whole genome bisulfite sequencing (WGBS) datasets for 16 tissues, 47 corresponding RNA-seq datasets, and 2 whole genome sequencing datasets. We did read mapping and DNA methylation calling based on two different cattle assemblies, demonstrating the high quality of the long-read-based assembly markedly improved DNA methylation results. We observed large differences across cattle tissues in the methylation patterns of global CpG sites, partially methylated domains (PMDs), hypomethylated regions (HMRs), CG islands (CGIs), and common repeats. We detected that each tissue had a distinct set of PMDs, which showed tissue-specific patterns. Similar to human PMD, cattle PMDs were often linked to a general decrease of gene expression and a decrease in active histone marks and related to long-range chromatin organizations, like topologically associated domains (TADs). We tested a classification of the HMRs based on their distributions relative to transcription start sites (TSSs) and detected tissue-specific TSS-HMRs and genes that showed strong tissue effects. When performing cross-species comparisons of paired genes (two opposite strand genes with their TSS located in the same HMR), we found out they were more consistently co-expressed among human, mouse, sheep, goat, yak, pig, and chicken, but showed lower consistent ratios in more divergent species. We further used these WGBS data to detect 50,023 experimentally supported CGIs across bovine tissues and found that they might function as a guard against C-to-T mutations for TSS-HMRs. Although common repeats were often heavily methylated, some young Bov-A2 repeats were hypomethylated in sperm and could affect the promoter structures by exposing potential transcription factor binding sites. This study provides a comprehensive resource for bovine epigenomic research and enables new discoveries about DNA methylation and its role in complex traits.en_US
dc.description.urihttps://doi.org/10.1186/s12915-020-00793-5
dc.identifierhttps://doi.org/10.13016/wv4s-t5kz
dc.identifier.citationZhou, Y., Liu, S., Hu, Y. et al. Comparative whole genome DNA methylation profiling across cattle tissues reveals global and tissue-specific methylation patterns. BMC Biol 18, 85 (2020).en_US
dc.identifier.urihttp://hdl.handle.net/1903/26941
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.relation.isAvailableAtCollege of Agriculture & Natural Resourcesen_us
dc.relation.isAvailableAtAnimal & Avian Sciencesen_us
dc.relation.isAvailableAtDigital Repository at the University of Marylanden_us
dc.relation.isAvailableAtUniversity of Maryland (College Park, MD)en_us
dc.subjectCattleen_US
dc.subjectSomatic tissuesen_US
dc.subjectDNA methylationen_US
dc.subjectPartially methylated domainsen_US
dc.subjectHypomethylated regionen_US
dc.subjectWGBS (whole genome bisulfite sequencing)en_US
dc.titleComparative whole genome DNA methylation profiling across cattle tissues reveals global and tissue-specific methylation patternsen_US
dc.typeArticleen_US

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