Comparative whole genome DNA methylation profiling of cattle sperm and somatic tissues reveals striking hypomethylated patterns in sperm

Abstract

BackgroundAlthough sperm DNA methylation has been studied in humans and other species, its status in cattle is largely unknown.ResultsUsing whole-genome bisulfite sequencing (WGBS), we profiled the DNA methylome of cattle sperm through comparison with three somatic tissues (mammary gland, brain, and blood). Large differences between cattle sperm and somatic cells were observed in the methylation patterns of global CpGs, pericentromeric satellites, partially methylated domains (PMDs), hypomethylated regions (HMRs), and common repeats. As expected, we observed low methylation in the promoter regions and high methylation in the bodies of active genes. We detected selective hypomethylation of megabase domains of centromeric satellite clusters, which may be related to chromosome segregation during meiosis and their rapid transcriptional activation upon fertilization. We found more PMDs in sperm cells than in somatic cells and identified meiosis-related genes such asKIF2B and REPIN1, which are hypomethylated in sperm but hypermethylated in somatic cells. In addition to the common HMRs around gene promoters, which showed substantial differences between sperm and somatic cells, the sperm-specific HMRs also targeted to distinct spermatogenesis-related genes, including BOLL, MAEL, ASZ1, SYCP3, CTCFL, MND1, SPATA22, PLD6, DDX4, RBBP8, FKBP6, and SYCE1. Although common repeats were heavily methylated in both sperm and somatic cells, some young Bov-A2 repeats, which belong to the SINE family, were hypomethylated in sperm and could affect the promoter structures by introducing new regulatory elements.ConclusionsOur study provides a comprehensive resource for bovine sperm epigenomic research and enables new discoveries about DNA methylation and its role in male fertility.

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“…They verified that global DNA methylation level in bull sperm is lower than other sperm species and, for the cell type comparison, sperm was less methylated than somatic cells. This hypomethylated profile of bovine sperm cell was also described in whole-genome bisulfite conversion analysis (ZHOU et al, 2018b). Overall, the percentage of methylation in our study, either in CpG context or CHG and CHH was low, in agree with other studies.…”

“…In the comparison between sex-sorted and conventional sperm samples, no difference was found for global methylation pattern, however individual differences were found for IGF2 and IGF2R, among bulls (CARVALHO et al, 2012). JIANG et al, 2018;ZHOU et al, 2018a). Overall, they agree that bull sperm is hypomethylated, unlike what is seen in humans, primates and mice (KOBAYASHI et al, 2012;MOLARO et al, 2011…”

“…In mice, the de novo methylation is established at embryonic day E13.5 in pro-spermatogonia and the methylome is complete prior to birth, and sustained though all spermatogenesis stages until mature spermatozoa (SEISENBERGER et al, 2012). Recently, the whole genome DNA methylation analysis in cattle showed that sperm presents a specific methylation pattern when compared to somatic cells (ZHOU et al, 2018a).…”

“…In regard DNA methylation, studies comparing sperm DNA with somatic cells verified that bovine sperm, differently of human sperm, is overall hypomethylatedZHOU et al, 2018a). For both studies, hypomethylated bull sperm DNA targeted processes relevant to germline differentiation and sperm function.…”

Integrating Signals from Sperm Methylome Analysis and Genome-Wide Association Study for a Better Understanding of Male Fertility in Cattle

“…We applied FastQC v 0.11.2 (https://www.bioinformatics.babraham.ac.uk/projects/fastqc/) and Trim Galore v 0.4.0 (https://www.bioinformatics.babraham.ac.uk/projects/trim_galore/) to evaluate the raw data quality and to filter the low-quality data, respectively [17]. Generally, the adapters were removed, and reads with low quality (Q < 20) and shorter than 20 bp were removed.…”