Imai Kenichi, Ochiai Kuniyasu
Department of Microbiology, Nihon University School of Dentistry, Tokyo, Japan.
J Oral Sci. 2011 Mar;53(1):1-13. doi: 10.2334/josnusd.53.1.
Although approximately 200 distinct cell types - including fibroblasts, neurons, and hematopoietic cells - possess the same DNA sequence, they have diverse functions in humans and exhibit considerably different gene expression patterns. It has become increasingly clear that epigenetic regulation plays an important role in gene expression. There are two major forms of epigenetic regulation: posttranslational modification of DNA-associated histone proteins in chromatin and methylation of DNA. These forms are regulated by distinct but coupled pathways. Notably, histone Lys acetylation by histone acetyltransferase and deacetylation by histone deacetylases play a crucial role in on-off regulation of gene expression. It is now understood that epigenetics plays an important role not only in the regulation of gene expression but also in the pathogenesis of a broad range of diseases such as cancer and microbial infections. We have determined that epigenetic regulation is involved in the establishment and maintenance of HIV-1 latency and in the reactivation of HIV-1 by periodontopathic bacteria. In this review, we focus on the effect of histone modification on transcriptional regulation and the contribution thereof to the regulation of HIV-1 gene expression during the lytic and latent stages of HIV-1 infection. Likewise, we discuss the mechanisms by which periodontal diseases may accelerate AIDS progression in infected individuals as a new systemic disease caused by periodontitis and describe potential therapeutic interventions based on epigenetic mechanisms.
尽管大约200种不同的细胞类型——包括成纤维细胞、神经元和造血细胞——拥有相同的DNA序列，但它们在人体中具有不同的功能，并表现出截然不同的基因表达模式。越来越清楚的是，表观遗传调控在基因表达中起着重要作用。表观遗传调控有两种主要形式：染色质中与DNA相关的组蛋白的翻译后修饰和DNA甲基化。这些形式由不同但相互关联的途径调控。值得注意的是，组蛋白乙酰转移酶介导的组蛋白赖氨酸乙酰化和组蛋白去乙酰化酶介导的去乙酰化在基因表达的开关调控中起关键作用。现在人们认识到，表观遗传学不仅在基因表达调控中起重要作用，而且在广泛的疾病如癌症和微生物感染的发病机制中也起重要作用。我们已经确定表观遗传调控参与了HIV-1潜伏状态的建立和维持以及牙周病原菌对HIV-1的激活。在这篇综述中，我们重点关注组蛋白修饰对转录调控的影响及其在HIV-1感染的裂解期和潜伏期对HIV-1基因表达调控的贡献。同样，我们讨论牙周疾病作为由牙周炎引起的一种新的全身性疾病可能加速感染个体艾滋病进展的机制，并描述基于表观遗传机制的潜在治疗干预措施。
