Baker Emilie C, San Audrey E, Cilkiz Kubra Z, Littlejohn Brittni P, Cardoso Rodolfo C, Ghaffari Noushin, Long Charles R, Riggs Penny K, Randel Ronald D, Welsh Thomas H, Riley David G
Department of Animal Science, Texas A&M University, College Station, TX 77845, USA.
Texas A&M AgriLife Research, College Station, TX 77845, USA.
Biology (Basel). 2023 Feb 5;12(2):252. doi: 10.3390/biology12020252.
Quantifying the natural inter-individual variation in DNA methylation patterns is important for identifying its contribution to phenotypic variation, but also for understanding how the environment affects variability, and for incorporation into statistical analyses. The inter-individual variation in DNA methylation patterns in female cattle and the effect that a prenatal stressor has on such variability have yet to be quantified. Thus, the objective of this study was to utilize methylation data from mature Brahman females to quantify the inter-individual variation in DNA methylation. Pregnant Brahman cows were transported for 2 h durations at days 60 ± 5; 80 ± 5; 100 ± 5; 120 ± 5; and 140 ± 5 of gestation. A non-transport group was maintained as a control. Leukocytes, amygdala, and anterior pituitary glands were harvested from eight cows born from the non-transport group (Control) and six from the transport group (PNS) at 5 years of age. The DNA harvested from the anterior pituitary contained the greatest variability in DNA methylation of cytosine-phosphate-guanine (mCpG) sites from both the PNS and Control groups, and the amygdala had the least. Numerous variable mCpG sites were associated with retrotransposable elements and highly repetitive regions of the genome. Some of the genomic features that had high variation in DNA methylation are involved in immune responses, signaling, responses to stimuli, and metabolic processes. The small overlap of highly variable CpG sites and features between tissues and leukocytes supports the role of variable DNA methylation in regulating tissue-specific gene expression. Many of the CpG sites that exhibited high variability in DNA methylation were common between the PNS and Control groups within a tissue, but there was little overlap in genomic features with high variability. The interaction between the prenatal environment and the genome could be responsible for the differences in location of the variable DNA methylation.
量化DNA甲基化模式中个体间的自然差异，对于确定其对表型变异的贡献很重要，同时对于理解环境如何影响变异性以及纳入统计分析也很重要。雌性牛DNA甲基化模式的个体间差异以及产前应激源对这种变异性的影响尚未得到量化。因此，本研究的目的是利用成年婆罗门雌性牛的甲基化数据来量化DNA甲基化的个体间差异。在妊娠第60±5天、80±5天、100±5天、120±5天和140±5天，将怀孕的婆罗门母牛运输2小时。设立一个非运输组作为对照。在5岁时，从非运输组（对照组）出生的8头母牛和运输组（PNS）出生的6头母牛中采集白细胞、杏仁核和垂体前叶。从垂体前叶提取的DNA在PNS组和对照组的胞嘧啶-磷酸-鸟嘌呤（mCpG）位点的DNA甲基化中具有最大的变异性，而杏仁核的变异性最小。许多可变的mCpG位点与反转录转座元件和基因组的高度重复区域有关。DNA甲基化变化较大的一些基因组特征参与免疫反应、信号传导、对刺激的反应和代谢过程。组织和白细胞之间高度可变的CpG位点和特征的小重叠支持了可变DNA甲基化在调节组织特异性基因表达中的作用。许多在DNA甲基化中表现出高变异性的CpG位点在组织内的PNS组和对照组之间是常见的，但在具有高变异性的基因组特征中几乎没有重叠。产前环境与基因组之间的相互作用可能是可变DNA甲基化位置差异的原因。
