Structural basis of nucleosome recognition by the human NuA4/TIP60 acetyltransferase complex

The human Tip60 histone acetyltransferase (HAT) complex, also known as the NuA4/TIP60 complex (TIP60-C), plays a crucial role in regulating chromatin accessibility. By linking histone acetylation with transcriptional activation and genome stability, the TIP60-C complex is a key player in metabolic regulation. However, the precise mechanism by which the catalytic HAT module interacts with its nucleosome substrate has remained unclear until now.

In this study, researchers have unveiled the structure of the human TIP60-C HAT module bound to a nucleosome. This discovery reveals a well-defined binding architecture, where TIP60, EPC1, ING3, and MEAF6 work together to position the catalytic center on the nucleosome surface. The HAT module is anchored to the histone acidic patch, enabling it to engage the linker DNA effectively.

The structural findings provide valuable insights into the intramolecular interaction involving the N-terminal Tudor domain of the TIP60 acetyltransferase subunit. This interaction suggests a potential mechanism for autoregulation of HAT activity. The researchers' work not only defines the core principles by which the human TIP60-C HAT module recognizes chromatin but also establishes a structural foundation for understanding how the TIP60-C complex modulates chromatin in metazoans.