Epigenetics is the study of how heritable changes in gene expression occur without changes in the DNA sequence itself. One important epigenetic mechanism is histone modification, which involves the addition or removal of chemical groups to histone proteins that DNA wraps around. This can alter the structure of the chromatin, which affects how genes are expressed.
HATs (histone acetyltransferases) are enzymes that add acetyl groups to histones, leading to a relaxation of the chromatin structure and increased gene expression. The structure and mechanism of HATs are not fully understood, limiting our ability to develop drugs that target these enzymes for therapeutic purposes.
In this breakthrough study, scientists used a combination of cryo-electron microscopy and molecular modeling to determine the 3D structure of the yeast NuA4 HAT complex, one of the best-studied HAT complexes. The structure revealed a remarkably complex architecture with multiple protein subunits arranged in a spiral staircase-like formation.
The study provides important insights into the mechanism of HATs and reveals how different subunits contribute to substrate recognition, catalysis, and regulation. The detailed structural understanding of NuA4 HAT complex opens up new avenues for the development of small molecules that modulate HAT activity, with potential applications in cancer therapy and other diseases where epigenetic dysregulation plays a role.
The findings also highlight the power of cryo-electron microscopy in studying large and dynamic macromolecular complexes involved in epigenetic regulation, paving the way for further discoveries in this exciting field of research.
