Sehrawat Parveen, Shobhawat Rahul, Kumar Ashutosh
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
Front Genet. 2022 Jul 14;13:903923. doi: 10.3389/fgene.2022.903923. eCollection 2022.
The fundamental packaging unit of chromatin, i.e., nucleosome, consists of ∼147 bp of DNA wrapped around a histone octamer composed of the core histones, H2A, H2B, H3, and H4, in two copies each. DNA packaged in nucleosomes must be accessible to various machineries, including replication, transcription, and DNA damage repair, implicating the dynamic nature of chromatin even in its compact state. As the tails protrude out of the nucleosome, they are easily accessible to various chromatin-modifying machineries and undergo post-translational modifications (PTMs), thus playing a critical role in epigenetic regulation. PTMs can regulate chromatin states charge modulation on histones, affecting interaction with various chromatin-associated proteins (CAPs) and DNA. With technological advancement, the list of PTMs is ever-growing along with their writers, readers, and erasers, expanding the complexity of an already intricate epigenetic field. In this review, we discuss how some of the specific PTMs on flexible histone tails affect the nucleosomal structure and regulate the accessibility of chromatin from a mechanistic standpoint and provide structural insights into some newly identified PTM-reader interaction.
染色质的基本包装单位，即核小体，由约147个碱基对的DNA缠绕在一个组蛋白八聚体上组成，该八聚体由核心组蛋白H2A、H2B、H3和H4各两个拷贝组成。包装在核小体中的DNA必须能够被各种机制所接近，包括复制、转录和DNA损伤修复，这意味着即使在其紧密状态下染色质也具有动态性质。由于组蛋白尾巴从核小体中伸出，它们很容易被各种染色质修饰机制所接近并经历翻译后修饰（PTM），因此在表观遗传调控中发挥着关键作用。PTM可以通过对组蛋白进行电荷调节来调控染色质状态，影响与各种染色质相关蛋白（CAP）和DNA的相互作用。随着技术的进步，PTM及其写入器、读取器和擦除器的种类不断增加，进一步扩大了这个本就错综复杂的表观遗传领域的复杂性。在这篇综述中，我们从机制的角度讨论了柔性组蛋白尾巴上的一些特定PTM如何影响核小体结构并调节染色质的可及性，并对一些新发现的PTM-读取器相互作用提供结构上的见解。
