Environmental influences in the establishment of the epigenetic landscape in children

环境对儿童表观遗传景观建立的影响

• 批准号: nhmrc : 437016
• 负责人: A/Pr Jeffrey Craig
• 金额: $ 46.35万
• 依托单位: Murdoch Childrens Research Institute
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Strategic Awards
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/environmental-influences-establishment-landscape-children/96775
• 关键词: Environmental; influences; establishment; epigenetic; landscape

The DNA in each of our cells does not exist alone, it is packaged into complex structures called chromosomes, through association with many different proteins. The distribution of these proteins varies along the length of a chromosome depending on the type of cell and this phenomenon is called 'epigenetics', literally meaning 'above the DNA'. Epigenetic analysis is the study of how proteins and other molecules can change the activity of a gene without changing the DNA sequence. All of our cells use epigenetic changes to help control how they grow and develop. Evidence suggests a direct link between diet and environmental influences on our epigenetic profile. Recent research has traced the origins of many of the health problems of adult life back to the earliest periods of development _ to the time spent in the womb and the first few years of life. If we are born with a low birth weight, we are more likely to get sick later in life. Overwhelming evidence exists that the environment in the womb is critical for a healthy birth weight (and health in later life) and it is thought that epigenetics may be the missing link between this environment, low birth weight, and therefore health in later life. In addition, mounting evidence supports a general link between epigenetic de-regulation and predisposition to disease. However, the timing and the overall contribution of environmental- genetic influences to the establishment of faulty epigenetic markings remain largely unknown. Twins are the best model to study this link as they share similar (but not identical environments) and some share identical genetic makeup. Using twins, Dr Jeffrey Craig and his team will investigate the factors in the prenatal environment that modify specific cells, leading to low birth weight and increase disease risk later in life. They predict that this occurs via specific changes in gene activity caused by epigenetic disruption.

我们每个细胞中的DNA并不是单独存在的，它通过与许多不同的蛋白质结合而被包装成称为染色体的复杂结构。这些蛋白质的分布沿着染色体的长度变化，这取决于细胞的类型，这种现象被称为“表观遗传学”，字面意思是“在DNA之上”。表观遗传分析是研究蛋白质和其他分子如何在不改变DNA序列的情况下改变基因的活性。我们所有的细胞都使用表观遗传变化来帮助控制它们的生长和发育。有证据表明，饮食和环境对我们的表观遗传特征的影响之间存在直接联系。最近的研究将成年生活中许多健康问题的根源追溯到最早的发育时期--在子宫里度过的时间和生命的最初几年。如果我们出生时体重较低，我们更有可能在以后的生活中生病。压倒性的证据表明，子宫内的环境对健康的出生体重（以及以后的健康）至关重要，并且认为表观遗传学可能是这种环境，低出生体重之间缺失的环节，因此在以后的生活中健康。此外，越来越多的证据支持表观遗传失调和疾病易感性之间的一般联系。然而，时间和环境遗传影响的总体贡献，以建立错误的表观遗传标记仍然在很大程度上是未知的。双胞胎是研究这种联系的最佳模型，因为他们共享相似（但不相同的环境），有些共享相同的基因组成。利用双胞胎，杰弗里克雷格博士和他的团队将调查产前环境中的因素，这些因素改变了特定的细胞，导致出生体重低，并增加了以后生活中的疾病风险。他们预测，这是通过表观遗传破坏引起的基因活性的特定变化而发生的。