Miller Jaime L, Grant Patrick A
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Subcell Biochem. 2013;61:289-317. doi: 10.1007/978-94-007-4525-4_13.
Although the field of genetics has grown by leaps and bounds within the last decade due to the completion and availability of the human genome sequence, transcriptional regulation still cannot be explained solely by an individual's DNA sequence. Complex coordination and communication between a plethora of well-conserved chromatin modifying factors are essential for all organisms. Regulation of gene expression depends on histone post translational modifications (HPTMs), DNA methylation, histone variants, remodeling enzymes, and effector proteins that influence the structure and function of chromatin, which affects a broad spectrum of cellular processes such as DNA repair, DNA replication, growth, and proliferation. If mutated or deleted, many of these factors can result in human disease at the level of transcriptional regulation. The common goal of recent studies is to understand disease states at the stage of altered gene expression. Utilizing information gained from new high-throughput techniques and analyses will aid biomedical research in the development of treatments that work at one of the most basic levels of gene expression, chromatin. This chapter will discuss the effects of and mechanism by which histone modifications and DNA methylation affect transcriptional regulation.
尽管在过去十年中，由于人类基因组序列的完成和可得性，遗传学领域取得了飞跃式发展，但转录调控仍不能仅由个体的DNA序列来解释。大量高度保守的染色质修饰因子之间复杂的协调和通讯对所有生物体来说都是必不可少的。基因表达的调控取决于组蛋白翻译后修饰（HPTMs）、DNA甲基化、组蛋白变体、重塑酶以及影响染色质结构和功能的效应蛋白，而染色质的结构和功能又会影响广泛的细胞过程，如DNA修复、DNA复制、生长和增殖。如果这些因子中的许多发生突变或缺失，可能会在转录调控水平导致人类疾病。近期研究的共同目标是在基因表达改变阶段理解疾病状态。利用从新的高通量技术和分析中获得的信息，将有助于生物医学研究开发在基因表达最基本层面之一——染色质层面起作用的治疗方法。本章将讨论组蛋白修饰和DNA甲基化影响转录调控的作用及机制。
