|ZHOU, YANG - Huazhong Agricultural University|
|LIU, SHULI - China Agricultural University|
|HU, YANG - Huazhong Agricultural University|
|FANG, LINGZHAO - University Of Edinburgh|
|GAO, YAHUI - University Of Maryland|
|XIA, HAN - Huazhong Agricultural University|
|Schroeder, Steven - Steve|
|CONNOR, ERIN - University Of Delaware|
|Baldwin, Ransom - Randy|
|Van Tassell, Curtis - Curt|
|YANG, LIGUO - Huazhong Agricultural University|
|MA, LI - University Of Maryland|
|Liu, Ge - George|
Submitted to: BMC Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/11/2020
Publication Date: 7/6/2020
Citation: Zhou, Y., Liu, S., Hu, Y., Fang, L., Gao, Y., Xia, H., Schroeder, S.G., Rosen, B.D., Connor, E.E., Li, C., Baldwin, R.L., Cole, J.B., Van Tassell, C.P., Yang, L., Ma, L., Liu, G. 2020. Comparative whole genome DNA methylation profiling of cattle tissues reveals global and tissue-specific methylation patterns. BMC Biology. 18(1):85. https://doi.org/10.1186/s12915-020-00793-5.
Interpretive Summary: DNA methylation plays important roles in tissue differentiation and normal development processes. We provided a comprehensive resource to study the landscapes of the DNA methylome across tissues in cattle. These results fill our knowledge gaps and provide the foundation for utilizing epignomic data from human and other model species for investigation of target species with less resources. Farmers, scientist, and policy planners who need improve animal health and production, as well as human health based on genomic data will benefit from this study.
Technical Abstract: Background: Although DNA methylation has been studied in humans and other species, its distribution patterns and regulatory impacts in cattle are still largely unknown. Results: Using Holstein cattle, we generated 29 whole genome bisulphite sequencing (WGBS) data for 16 tissues, 47 corresponding RNA-seq data, and 4 whole genome sequencing data. We observed large differences among cattle tissues in the methylation patterns of global CpG sites, partially methylated domains (PMD), hypomethylated regions (HMR), CG Islands (CGI), and common repeats. We detected that cattle PMDs were present in up to 50% of the genome across these tissues and their lowest level of methylation was observed in placenta. Cattle PMDs were often linked to a general decrease of gene expression, an increase in heterochromatic histone marks and correlated with long-range chromatin organizations, like TADs (topologically associated domains). Each tissue had a distinct set of PMDs, within which expressed genes showed tissue-specific effects. We tested a classification of the HMRs based on their distributions relative to transcription start sites (TSS) and detected tissue-specific TSS-HMR showed strong tissue effects. We also experimentally defined CGI across bovine tissues and found that they 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. Conclusions: This study provides a comprehensive resource for bovine epigenomic research and enables new discoveries about DNA methylation and its role in complex traits.