Epigenetic changes in gene expression: focus on "The liver X-receptor gene promoter is hypermethylated in a mouse model of prenatal protein restriction".
Epigenetic changes in gene expression: focus on "The liver X-receptor gene promoter is hypermethylated in a mouse model of prenatal protein restriction".
复制标题
基因表达的表观遗传变化：关注“肝脏X受体基因启动子在产前蛋白质限制的小鼠模型中高度甲基化”。
DOI：
10.1152/ajpregu.00760.2009
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Alexander,BarbaraT
中科院分区：
文献类型：
--
作者：
Alexander,BarbaraT
表型遗传学一词最早由Waddington于1942年提出，用来描述发育过程中基因与环境的相互作用，从而产生表型。今天，术语表观遗传学用于描述以常规遗传相互作用之外的方式发生的表型，指不涉及DNA序列变化的基因表达的稳定和可遗传的改变（9）。DNA甲基化是一种表观遗传机制，作为复制后修饰，可响应环境影响而发生（14）。DNA甲基化涉及二核苷酸序列CpG中发现的胞嘧啶的修饰（9），可以激活或抑制转录，是可逆的（9），并且在正常哺乳动物细胞分化和发育中发挥关键作用（14）。DNA甲基化也与许多年龄相关疾病的病理学有关，如癌症（6），重要的是，基因组的表观遗传修饰可以使基因活性稳定地传递给下一代（9）。健康和疾病的发育起源（DOHaD）是指胎儿的表型因环境影响而改变的过程（2）。DOHaD假说起源于婴儿死亡率和缺血性心脏病的地理相关性（2）。基于这项研究，Barker（2）提出，早期发育期间的不良环境影响永久性地改变了身体的结构，功能和代谢，导致成年心血管和代谢疾病的风险增加。许多流行病学研究现在证实了这种关联，许多实验研究已经调查了DOHaD的潜在机制;然而，胎儿生命和程序性成人疾病之间的确切联系仍不清楚。虽然在暴露于环境压力的胎儿中观察到的成人健康和疾病的风险增加暗示表观遗传过程是一种可能的联系（图1），但很少有研究直接验证这一假设。母体低蛋白的啮齿动物模型被充分描述为DOHaD的实验模型（10）。蛋白质是胎儿正常生长的关键（3），母体饮食中蛋白质含量从18%至20%减少到9%至12%可能导致胎儿生长不成比例，高血压，心血管疾病和低蛋白后代的代谢程序（1，3，10，19）。此外，出生体重下降（3），心血管功能障碍（19）和肝脏基因启动子甲基化的程序性改变（4）可以延伸到下一代。因此，
THE TERM EPIGENETICS WAS FIRST coined in 1942 by Waddington (20) to describe the interaction of genes with their environment during development that gives rise to a phenotype. Today, the term epigenetics is used when describing a phenotype that occurs in a manner outside conventional genetic interactions and refers to stable and heritable alterations in gene expression that do not involve a change in DNA sequence (9). DNA methylation is one type of epigenetic mechanism that serves as a postreplication modification and can occur in response to environmental influences (14). DNA methylation, which involves the modification of cytosines found in the dinucleotide sequence CpG (9), can activate or suppress transcription, is reversible (9), and plays a critical role in normal mammalian cell differentiation and development (14). DNA methylation is also implicated in the pathology of many age-related diseases, such as cancer (6), and, importantly, epigenetic modification of the genome can allow for stable transmission of gene activity to the next generation (9).Developmental origins of health and disease (DOHaD) refers to the process by which the phenotype of a fetus is altered in response to environmental influences (2). The DOHaD hypothesis originated from a geographical correlation of infant mortality and ischemic heart disease (2). Based on this study, Barker (2) proposed that adverse environmental influences during early development permanently alter the body’s structure, function, and metabolism in ways that lead to an increased risk for adult cardiovascular and metabolic disease. Numerous epidemiological studies now validate this association, and numerous experimental studies have investigated potential mechanisms involved in the DOHaD (1); however, the exact link between fetal life and programmed adult disease remains unclear. Although the increased risk of adult health and disease observed in a fetus exposed to environmental stresses implicates epigenetic processes as a possible link (Figure 1), few studies have directly tested this hypothesis. The rodent model of maternal low protein is well characterized as an experimental model of DOHaD (10). Protein is key for proper fetal growth (3) and a reduction in protein content from a range of 18% to 20% to a range of 9% to 12% in the maternal diet can lead to disproportionate fetal growth, hypertension, cardiovascular disease, and metabolic programming in low-protein offspring (1, 3, 10, 19). In addition, reductions in birth weight (3), cardiovascular dysfunction (19), and programmed alterations in methylation of hepatic gene promoters (4) can extend to the next generation. Thus, the mechanism by
影响因子：
3.8
作者：
Plosch, T.;van Straten, E. M. E.;Kuipers, F.
通讯作者：
Kuipers, F.