A Conserved Function for the H2A.Z C Terminus

Histone H2A variants generate diversity in chromatin structure and functions, as nucleosomes containing variant H2A histones have altered physical, chemical, and biological properties. H2A.Z is an evolutionarily ancient and highly conserved H2A variant that regulates processes ranging from gene expression to the DNA damage response. Here we find that the unstructured portion of the C-terminal tail of H2A.Z is required for the normal functions of this histone variant in budding yeast. We have also identified a novel splice isoform of the human H2A.Z-2 gene that encodes a C-terminally truncated H2A.Z protein that is similar to the truncation mutants we identified in yeast. The short forms of H2A.Z in both yeast and human cells are more loosely associated with chromatin than the full-length proteins, indicating a conserved function for the H2A.Z C-terminal tail in regulating the association of H2A.Z with nucleosomes. The H2A variant H2A.Z is an important regulatory component of chromatin. A novel form of human H2A.Z and mutants of yeast H2A.Z that share truncated C termini have altered properties. The C-terminal tail of histone H2A.Z is important for its stable association with nucleosomes. The strength of H2A.Z's association with nucleosomes is key to the biological functions of this histone variant.