Furumatsu Takayuki, Ozaki Toshifumi
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Detistry and Pharmaceucial Sciences, Okayama 700-8558, Japan.
Acta Med Okayama. 2010 Jun;64(3):155-61. doi: 10.18926/AMO/40007.
Epigenetics is an essential mechanism to control gene expression and fundamental cellular processes. DNA methylation in CpG-rich promoters correlates with gene silencing. Histone modification including histone acetylation and deacetylation determines the stability of the chromatin structure. Condensed chromatin (heterochromatin), which has a higher-order histone-DNA structure, prevents the access of transcriptional activators to their target genes. The fundamental unit of eukaryotic chromatin consists of 146 bp of DNA wrapped around a histone octamer. Posttranslational modifications of the histone tail and the chromatin remodeling complex disrupt histone-DNA contacts and induce nucleosome mobilization. Histone acetylation of specific lysine residues in the histone tail plays a crucial role in epigenetic regulation. Histone acetylation is a dynamic process regulated by the antagonistic actions of 2 families of enzymes - the histone acetyltransferases (HATs) and the histone deacetylases (HDACs). The balance between histone acetylation and deacetylation serves as a key epigenetic mechanism for transcription factor-dependent gene expression and the developmental process. We review emerging evidence that DNA methylation, histone acetylation modified by HAT and/or HDAC, and transcription factor-associated molecules contribute to a mechanism that can alter chromatin structure, gene expression, and cellular differentiation during chondrogenesis.
表观遗传学是控制基因表达和基本细胞过程的重要机制。富含CpG的启动子中的DNA甲基化与基因沉默相关。包括组蛋白乙酰化和去乙酰化在内的组蛋白修饰决定了染色质结构的稳定性。具有高阶组蛋白-DNA结构的浓缩染色质（异染色质）阻止转录激活因子与其靶基因的结合。真核染色质的基本单位由缠绕在组蛋白八聚体上的146 bp DNA组成。组蛋白尾巴的翻译后修饰和染色质重塑复合物破坏组蛋白-DNA接触并诱导核小体移动。组蛋白尾巴中特定赖氨酸残基的组蛋白乙酰化在表观遗传调控中起关键作用。组蛋白乙酰化是一个由两类酶——组蛋白乙酰转移酶（HATs）和组蛋白去乙酰化酶（HDACs）的拮抗作用调节的动态过程。组蛋白乙酰化和去乙酰化之间的平衡是转录因子依赖性基因表达和发育过程的关键表观遗传机制。我们综述了新出现的证据，即DNA甲基化、由HAT和/或HDAC修饰的组蛋白乙酰化以及与转录因子相关的分子促成了一种在软骨形成过程中可改变染色质结构、基因表达和细胞分化的机制。
