近期发表在Journal of Dental Research上的一篇关于表观遗传学在口腔生物学中的意义的综述报道。遗传信息的编码不仅取决于线性的DNA序列，而且还会经染色质结构进行表观遗传学修改，如DNA甲基化和与DNA结合蛋白的共价修饰。这些“表观遗传学”可以通过改变染色质的结构来影响基因的表达。自然发生的甲基化通常在CpG序列的胞嘧啶碱基上，他参与了基因正确表达的控制。
DNA甲基化通常与组蛋白脱乙酰化、染色质浓缩和基因沉默相关，染色质浓缩，和基因沉默。不同的甲基化可引起不同的组织模式和疾病差异。这种甲基化可变位点并非均匀分布在整个基因组，而是集中在某些基因，这些基因进行基因转录、生长、代谢、分化和癌变的调控。甲基化状态可产生表观遗传学改变。环境压力包括有毒物质，以及微生物和病毒的接触，也可以改变表观遗传学，从而改变基因活化和细胞表型。由于DNA甲基化往往是继随与细胞分裂，甲基化可变位点的积累，并随着时间的推移可能会导致细胞代谢稳态、对刺激的反应等持续的改变，或者会保留的异常表型。因此， DNA的表观遗传学依然是遗传、疾病和环境之间主要和以前缺少研究的环节。口腔生物学面临的挑战是加强这种机制的理解，确定表观遗传学在疾病发病机制或治疗响应的作用。（生物谷Bioon.com）
生物谷推荐原始出处：
Journal of Dental Research, Vol. 88, No. 5, 400-408 (2009) DOI: 10.1177/0022034509335868
Epigenetics: Connecting Environment and Genotype to Phenotype and Disease
S.P. Barros* and S. Offenbacher
Center for Oral and Systemic Diseases, Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill, Room 222, CB 7455, Chapel Hill, NC, USA 27599
Genetic information is encoded not only by the linear sequence of DNA, but also by epigenetic modifications of chromatin structure that include DNA methylation and covalent modifications of the proteins that bind DNA. These "epigenetic marks" alter the structure of chromatin to influence gene expression. Methylation occurs naturally on cytosine bases at CpG sequences and is involved in controlling the correct expression of genes. DNA methylation is usually associated with triggering histone deacetylation, chromatin condensation, and gene silencing. Differentially methylated cytosines give rise to distinct patterns specific for each tissue type and disease state. Such methylation-variable positions (MVPs) are not uniformly distributed throughout our genome, but are concentrated among genes that regulate transcription, growth, metabolism, differentiation, and oncogenesis. Alterations in MVP methylation status create epigenetic patterns that appear to regulate gene expression profiles during cell differentiation, growth, and development, as well as in cancer. Environmental stressors including toxins, as well as microbial and viral exposures, can change epigenetic patterns and thereby effect changes in gene activation and cell phenotype. Since DNA methylation is often retained following cell division, altered MVP patterns in tissues can accumulate over time and can lead to persistent alterations in steady-state cellular metabolism, responses to stimuli, or the retention of an abnormal phenotype, reflecting a molecular consequence of gene-environment interaction. Hence, DNA epigenetics constitutes the main and previously missing link among genetics, disease, and the environment. The challenge in oral biology will be to understand the mechanisms that modify MVPs in oral tissues and to identify those epigenetic patterns that modify disease pathogenesis or responses to therapy.
