Selective breeding has been utilized to study the genetic basis of exercise behavior, but research suggests that epigenetic mechanisms, such as DNA methylation, also contribute to this behavior. In a previous study, we demonstrated that the brains of mice from a genetically selected high runner (HR) line have sex-specific changes in DNA methylation patterns in genes known to be genomically imprinted compared to those from a non-selected control (C) line. Through cross-fostering, we also found that maternal upbringing can modify the DNA methylation patterns of additional genes. Here, we identify an additional set of genes in which DNA methylation patterns and gene expression may be altered by selection for increased wheel-running activity and maternal upbringing. We performed bisulfite sequencing and gene expression assays of 14 genes in the brain and found alterations in DNA methylation and gene expression for Bdnf, Pde4d and Grin2b. Decreases in Bdnf methylation correlated with significant increases in Bdnf gene expression in the hippocampus of HR compared to C mice. Cross-fostering also influenced the DNA methylation patterns for Pde4d in the cortex and Grin2b in the hippocampus, with associated changes in gene expression. We also found that the DNA methylation patterns for Atrx and Oxtr in the cortex and Atrx and Bdnf in the hippocampus were further modified by sex. Together with our previous study, these results suggest that DNA methylation and the resulting change in gene expression may interact with early-life influences to shape adult exercise behavior.

中文翻译：

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母体养育和自愿运动行为的选择性育种改变了小鼠大脑中 DNA 甲基化和基因表达的模式

选择性育种已被用来研究运动行为的遗传基础，但研究表明，表观遗传机制（例如 DNA 甲基化）也有助于这种行为。在之前的一项研究中，我们证明，与来自非选择对照的小鼠相比，来自基因选择的高跑者 (HR) 品系的小鼠大脑中已知基因组印记基因的 DNA 甲基化模式存在性别特异性变化 (C)线。通过交叉寄养，我们还发现母性养育可以改变其他基因的 DNA 甲基化模式。在这里，我们确定了一组额外的基因，其中 DNA 甲基化模式和基因表达可能会通过增加轮子运行活动和母性养育的选择而改变。我们对大脑中的 14 个基因进行了亚硫酸氢盐测序和基因表达测定，发现Bdnf、Pde4d和Grin2b的 DNA 甲基化和基因表达发生了变化。与 C 小鼠相比，HR 海马中Bdnf甲基化的减少与Bdnf基因表达的显着增加相关。交叉寄养还影响了皮质中Pde4d和海马体中Grin2b的 DNA 甲基化模式，以及相关的基因表达变化。我们还发现，皮质中的Atrx和Oxtr以及海马体中的Atrx和Bdnf的 DNA 甲基化模式进一步因性别而改变。结合我们之前的研究，这些结果表明 DNA 甲基化和由此产生的基因表达变化可能与生命早期的影响相互作用，从而塑造成人的运动行为。