哺乳动物基因组在原始生殖细胞的建立过程中和受精后的植入前胚胎中经历两个全局表观遗传重编程事件。这些事件涉及DNA甲基化标记的擦除和重建。然而,印迹基因和转座因子(TEs)保持其DNA甲基化特征,以确保正常的胚胎发育和基因组稳定性。尽管在小鼠和人类中进行了广泛的研究,关于环境诱导的表观遗传标记,在其他物种中逃避表观遗传重编程的知识有限。因此,这项研究的目的是研究绵羊基因组区域的特征和位置,逃避表观遗传重编程,以及探索这些区域内基因的生物学功能。在之前的研究中,我们在F1代和F2代鉴定了107个跨代遗传差异甲基化胞嘧啶(DMC),以响应父代补充蛋氨酸的饮食.这些DMC是在TE中发现的,非重复区域,以及印迹和非印迹基因。我们的发现表明基因组区域,而不是TEs和印记基因,有逃避重编程的倾向,并作为跨代表观遗传的潜在候选者。值得注意的是,34个受父系营养影响的跨代甲基化基因逃脱了重编程,影响增长,发展,男性生育能力,心脏病,和神经发育。有趣的是,在这些基因中,21与神经发育和脑部疾病有关,比如自闭症,精神分裂症,双相情感障碍,智力残疾。这表明大脑和不育疾病之间存在潜在的遗传重叠。总的来说,我们的研究支持哺乳动物环境诱导标记的跨代表观遗传的概念。
The mammalian genome undergoes two global epigenetic reprogramming events during the establishment of primordial germ cells and in the pre-implantation embryo after fertilization. These events involve the erasure and re-establishment of DNA methylation marks. However, imprinted genes and transposable elements (TEs) maintain their DNA methylation signatures to ensure normal embryonic development and genome stability. Despite extensive research in mice and humans, there is limited knowledge regarding environmentally induced epigenetic marks that escape epigenetic reprogramming in other species. Therefore, the objective of this study was to examine the characteristics and locations of genomic regions that evade epigenetic reprogramming in sheep, as well as to explore the biological functions of the genes within these regions. In a previous study, we identified 107 transgenerationally inherited differentially methylated cytosines (DMCs) in the F1 and F2 generations in response to a paternal methionine-supplemented diet. These DMCs were found in TEs, non-repetitive regions, and imprinted and non-imprinted genes. Our findings suggest that genomic regions, rather than TEs and imprinted genes, have the propensity to escape reprogramming and serve as potential candidates for transgenerational epigenetic inheritance. Notably, 34 transgenerational methylated genes influenced by paternal nutrition escaped reprogramming, impacting growth, development, male fertility, cardiac disorders, and neurodevelopment. Intriguingly, among these genes, 21 have been associated with neural development and brain disorders, such as autism, schizophrenia, bipolar disease, and intellectual disability. This suggests a potential genetic overlap between brain and infertility disorders. Overall, our study supports the concept of transgenerational epigenetic inheritance of environmentally induced marks in mammals.