Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPAR alpha promoter of the offspring.
Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPAR alpha promoter of the offspring.
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DOI：
10.1017/s0007114507894438
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发表时间：
2008-08
影响因子：
3.6
通讯作者：
Burdge, Graham C.
中科院分区：
文献类型：
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作者：
Lillycrop, Karen A.;Phillips, Emma S.;Torrens, Christopher;Hanson, Mark A.;Jackson, Alan A.;Burdge, Graham C.
产前营养不良引起的表型改变涉及特定基因的表观遗传调控的变化。我们研究了给孕鼠喂食含有不同量叶酸的蛋白质限制（PR）饮食对幼年后代肝脏PPARα启动子中单个CpG二核苷酸甲基化的影响，以及母体PR饮食对成年后代CpG甲基化的影响。孕鼠（n 5 /组）分别饲喂180 g/ kg酪蛋白（对照组）或90 g/ kg酪蛋白（PR组）和1 mg/ kg叶酸（叶酸组），或90 g/ kg酪蛋白和5 mg / kg叶酸（PRF组）。在出生后第34天（n 5只雄性和雌性/组）和第80天（n 5只雄性/组）处死后代。通过焦磷酸测序法测定PPARα启动子中16个CpG二核苷酸的甲基化。PR后代的平均PPARα启动子甲基化（4.5%）比对照组（6.1%）低26%，这是由于CpG二核苷酸2（40%）、3（43%）、4（33%）和16（48%）的特异性减少（P < 0.05）。在对照和PRF后代之间，这些CpG的甲基化没有显著差异。PRF后代中CpGs 5和8的甲基化程度高于对照或PR后代（分别为47%和63%，P < 0.05）。第80天PR后代的甲基化模式与第34天PR后代相当。这些数据首次表明，产前营养诱导不同的变化，个别CpG二核苷酸甲基化在幼年大鼠，持续在成年。
Induction of an altered phenotype by prenatal under-nutrition involves changes in the epigenetic regulation of specific genes. We investigated the effect of feeding pregnant rats a protein-restricted (PR) diet with different amounts of folic acid on the methylation of individual CpG dinucleotides in the hepatic PPARα promoter in juvenile offspring, and the effect of the maternal PR diet on CpG methylation in adult offspring. Pregnant rats (n 5 / group) were fed 180g / kg casein (Control) or 90g / kg casein (PR) with 1mg / kg folic acid, or 90g / kg casein and 5 mg / kg folic acid (PRF). Offspring were killed on postnatal d34 (n 5 males and females / group) and d80 (n 5 males / group). Methylation of 16 CpG dinucleotides in the PPARα promoter was measured by pyrosequencing. Mean PPARα promoter methylation in the PR offspring (4.5%) was 26% lower than Controls (6.1%) due to specific reduction at CpG dinucleotides 2 (40%), 3 (43%), 4 (33%) and 16 (48 %) (P < 0.05). There was no significant difference in methylation at these CpGs between Control and PRF offspring. Methylation of CpGs 5 and 8 was higher (47% and 63%, respectively, P < 0.05) in the PRF offspring than Control or PR offspring. The methylation pattern in d80 PR offspring was comparable to d34 PR offspring. These data show for the first time that prenatal nutrition induces differential changes to the methylation of individual CpG dinucleotides in juvenile rats which persist in adults.