Experimental HTS, SRB-3, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612-9416, USA.
Clin Rev Allergy Immunol. 2012 Feb;42(1):58-70. doi: 10.1007/s12016-011-8290-y.
Genetics and environmental factors have important roles in autoimmune diseases but neither has given us sufficient understanding of these mysterious diseases. Therefore, we are now looking closer at epigenetics, an interface between genetics and environmental factors. Epigenetics can be defined as reversible heritable changes to chromatin that can alter gene expression without altering the gene's DNA sequence. Methylation of DNA and histones are primary means of epigenetic control. By adding methyl groups to DNA and histones, it can limit accessibility of the underlying gene thereby altering the amount of gene expression. The methyl group is derived from an essential molecule in the cell, S-adenosylmethionine (SAM). However, a group of small molecules called polyamines also require SAM for their synthesis. Polyamines are essential for many cellular functions and polyamine activity is increased in many autoimmune diseases. Presented here is the "polyamine hypothesis" in which increased polyamine synthesis competes with cellular methylation (epigenetic control) for SAM. It is proposed that increased polyamine activity can cause disruption of cellular methylation, which can lead to abnormal expression of previously sequestered genes and disruption of other methylation-dependent cellular processes.
遗传和环境因素在自身免疫性疾病中起着重要作用，但两者都没有让我们充分了解这些神秘的疾病。因此，我们现在更关注表观遗传学，这是遗传和环境因素之间的一个接口。表观遗传学可以定义为染色质的可逆遗传变化，它可以改变基因表达而不改变基因的 DNA 序列。DNA 和组蛋白的甲基化是表观遗传调控的主要手段。通过向 DNA 和组蛋白添加甲基基团，可以限制潜在基因的可及性，从而改变基因表达的量。甲基基团来自细胞中的一种必需分子，即 S-腺苷甲硫氨酸 (SAM)。然而，一组称为多胺的小分子也需要 SAM 来合成。多胺对许多细胞功能至关重要，并且在许多自身免疫性疾病中多胺活性增加。本文提出了“多胺假说”，其中多胺的合成增加与细胞甲基化（表观遗传控制）竞争 SAM。据推测，多胺活性的增加会导致细胞甲基化的破坏，从而导致先前隔离的基因异常表达，并破坏其他依赖甲基化的细胞过程。
