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首页> 外文期刊>The Journal of Nutritional Biochemistry >Histone modifications, not DNA methylation, cause transcriptional repression of p16 (CDKN2A) in the mammary glands of offspring of protein-restricted rats.
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Histone modifications, not DNA methylation, cause transcriptional repression of p16 (CDKN2A) in the mammary glands of offspring of protein-restricted rats.

机译：组蛋白修饰而不是DNA甲基化会导致蛋白质受限大鼠后代的乳腺中p16（CDKN2A）的转录抑制。

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摘要

Maternal nutrition during pregnancy is an important intrauterine factor that results in persistent alteration of the offspring epigenome and that associates with health outcome in later life. This study examined the effect of maternal low-protein diet on the regulation of the p16 cell-cycle gene expression in the mammary gland of offspring rats. Timed-pregnant Sprague-Dawley rats were fed during gestation one of two isocaloric diets, control (18% casein) or low protein (LP, 9% casein). The expression of p16 mRNA in the mammary gland of the LP offspring was decreased by 75% vs. control. We also detected decreased p16 protein content in the mammary glands of pups gestated under the LP diet. Analysis of transcriptional and epigenetic regulation in offspring rats with maternal LP diet revealed the regulatory mechanisms underlying decreased p16 expression. Chromatin immunoprecipitation (ChIP) assay demonstrated that the altered p16 mRNA level and transcription rate in LP offspring resulted from histone code changes, including the reduced acetylation of histone H4 and the dimethylation of histone H3 at lysine 4 residues within the p16 promoter region. These results supported the hypothesis that maternal protein restriction during pregnancy programs p16 expression through histone code alterations in offspring mammary gland. Copyright Copyright 2011 Elsevier Inc. All rights reserved.
机译：怀孕期间的孕产妇营养是重要的子宫内因素，会导致后代表观基因组的持续改变，并与以后的健康状况相关。这项研究检查了母体低蛋白饮食对子代大鼠乳腺中p16细胞周期基因表达的调节作用。在妊娠期间给定时怀孕的Sprague-Dawley大鼠喂食两种等热量饮食之一，即对照（18％酪蛋白）或低蛋白（LP，9％酪蛋白）。与对照组相比，LP后代的乳腺中p16 mRNA的表达降低了75％。我们还发现在LP饮食下怀孕的幼崽的乳腺中p16蛋白含量降低。分析具有母体LP饮食的后代大鼠的转录和表观遗传调控，揭示了p16表达降低的调控机制。染色质免疫沉淀（ChIP）分析表明，LP后代中p16 mRNA水平和转录率的改变是由组蛋白编码变化引起的，包括组蛋白H4的乙酰化降低和组蛋白H3在p16启动子区域内赖氨酸4残基处的二甲基化。这些结果支持这样的假说：怀孕期间的母体蛋白质限制通过后代乳腺中的组蛋白编码改变来编程表达p16。版权版权所有2011 Elsevier Inc.保留所有权利。

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