A gestational low-protein diet represses p21(WAF1/Cip1) expression in the mammary gland of offspring rats through promoter histone modifications.
A gestational low-protein diet represses p21(WAF1/Cip1) expression in the mammary gland of offspring rats through promoter histone modifications.
复制标题
妊娠低蛋白饮食通过启动子组蛋白修饰抑制子代大鼠乳腺中 p21（WAF1/Cip1）的表达。
DOI：
10.1017/s0007114511006222
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Pan,Yuan-Xiang
中科院分区：
文献类型：
--
作者：
Zheng,Shasha;Rollet,Michelle;Yang,Kefeng;Pan,Yuan-Xiang
母亲在怀孕期间暴露于环境因素可能会改变后代乳腺发育过程中的某些代谢过程，并改变表观基因组。这可能使后代在以后的生活中更容易患乳腺癌。本研究的目的是研究母体蛋白限制对大鼠后代乳腺细胞周期蛋白依赖性激酶抑制剂1 （p21）基因表达调控的影响。定时交配的Sprague-Dawley大鼠在妊娠期间被喂食两种等能饲料中的一种，对照（C， 18%酪蛋白）或低蛋白（LP， 9%酪蛋白）。与C组相比，LP子代乳腺p21 mRNA和蛋白水平均下降。染色质免疫沉淀实验表明，LP后代p21转录下调与p21启动子区域组蛋白H3乙酰化和H3K4二甲基化减少有关，但与组蛋白H4乙酰化或组蛋白甲基化无关。使用亚硫酸盐测序的DNA甲基化分析未检测到C组和LP组后代之间p21启动子甲基化的差异。我们得出结论，母体蛋白限制通过p21基因启动子区域的组蛋白修饰抑制子代乳腺中p21基因的表达。
Maternal exposure to environmental agents throughout pregnancy may change certain metabolic processes during the offspring's mammary gland development and alter the epigenome. This may predispose the offspring to breast cancer later in life. The purpose of the present study was to examine the effect of maternal protein restriction on the regulation of cyclin-dependent kinase inhibitor 1 (p21) gene expression in the mammary gland of rat offspring. Timed-mated Sprague–Dawley rats were fed one of the two isoenergetic diets, control (C, 18 % casein) or low protein (LP, 9 % casein), during gestation. Compared with the C group, LP offspring showed a decrease of p21 in the mammary gland at both the mRNA and protein levels. Chromatin immunoprecipitation assay demonstrated that the down-regulation of p21 transcription in LP offspring was associated with reduced acetylation of histone H3 and dimethylation of H3K4 within the p21 promoter region, but was not associated with acetylation of histone H4 or histone methylation. DNA methylation analysis using bisulphite sequencing did not detect differences in methylation at the p21 promoter between the offspring of the C and LP groups. We conclude that maternal protein restriction inhibits p21 gene expression in the mammary gland of offspring through histone modifications at the promoter region of the p21 gene.