Mechanism of Histone Variant H2A.Z Deposition by SWR1-Com

DNA, which is packaged into highly condensed structures in the cell, carries genetic information that is passed from one generation to the next. Chromatin is the first level of DNA packaging that eventually results in the formation of chromosomes – threadlike parts of a cell that carry hereditary information in the form of genes. Many debilitating and life-threatening diseases, such as cancer, neurodegenerative diseases including Alzheimer's and Huntington's, and inherited childhood syndromes, result not only from changes in the basic DNA sequence, but also from changes in the structure of chromatin. DNA is condensed into chromatin with the help of DNA-packaging proteins called histones. DNA wraps around eight core histones – two each of H2A, H2B, H3, and H4 – to assemble into chromatin. H2A.Z is a variant of the core histone H2A that is conserved through evolution. Structurally, H2A.Z is different toward the end of the protein. A large protein complex called SWR1-Com, which binds to H2A.Z but doesn’t bind H2A, deposits H2A.Z into chromatin. Alice Wang is researching the differences between the way H2A.Z and H2A are deposited into chromatin. She is specifically investigating whether the difference between H2A and H2A.Z lies in their different binding capabilities to SWR1-Com. The findings will help increase understanding of H2A.Z biology and how chromosomal neighbourhoods containing H2A.Z are made. Wang’s ultimate aims for the research is to contribute to development of therapies for diseases that result from changes in chromatin structure.