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人类疾病的基因-环境相互作用及表观遗传基础。

Gene-environment interactions and epigenetic basis of human diseases.

作者信息

Liu Liang, Li Yuanyuan, Tollefsbol Trygve O

机构信息

Department of Medicine, University of Alabama at Birmingham, AL, USA.

出版信息

Curr Issues Mol Biol. 2008;10(1-2):25-36.

Abstract

Most human diseases are related in some way to the loss or gain in gene functions. Regulation of gene expression is a complex process. In addition to genetic mechanisms, epigenetic causes are gaining new perspectives in human diseases related to gene deregulation. Most eukaryotic genes are packed into chromatin structures, which lead to high condensations of the genes that require dynamic chromatin remodeling processes to facilitate their transcription. DNA methylation and histone modifications represent two of the major chromatin remodeling processes. They also serve to integrate environmental signals for the cells to modulate the functional output of their genome. Complex human diseases such as cancer and type 2 diabetes are believed to have a strong environmental component in addition to genetic causes. Aberrancies in chromatin remodeling are associated with both genetically and environmentally-related diseases. We will focus on recent findings of the epigenetic basis of human metabolic disorders to facilitate further exploration of epigenetic mechanisms and better understandings of the molecular cues underlying such complex diseases.

摘要

大多数人类疾病在某种程度上与基因功能的丧失或获得有关。基因表达的调控是一个复杂的过程。除了遗传机制外,表观遗传因素在与基因失调相关的人类疾病中也获得了新的研究视角。大多数真核基因被包装成染色质结构,这导致基因高度浓缩,需要动态的染色质重塑过程来促进其转录。DNA甲基化和组蛋白修饰是两种主要的染色质重塑过程。它们还用于整合环境信号,使细胞能够调节其基因组的功能输出。诸如癌症和2型糖尿病等复杂的人类疾病,除了遗传因素外,还被认为具有很强的环境因素。染色质重塑异常与遗传和环境相关疾病都有关联。我们将关注人类代谢紊乱表观遗传基础的最新研究成果,以促进对表观遗传机制的进一步探索,并更好地理解这些复杂疾病背后的分子线索。

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