Catching Nucleosome by Its Decorated Tails Determines Its Functional States

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 via 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.