Grant: Operating Grant

H2A.Z is a histone variant that replaces core histone H2A at specific parts of the genome. Previous studies have validated that H2A.Z plays a critical role in controlling gene expression at the transcription level. Moreover, overexpression of H2A.Z has been linked to oncogenesis, suggesting that excessive or mis-regulated H2A.Z can drive cancer development. More recent studies showed that there in fact 2 distinct isoforoms of H2A.Z that differ only by 3 amino acids. At present, whether these 2 H2A.Z isoforms have distinct or redundant functions is not well understood. We have discovered several distinctive differences between these two isoforms that support the current thought that they are not functionally equivalent. We will use a number of genome-wide methods, as well as our in-lab developed nucleosome purification-proteomics approach to further dissect the functional differences of these two isoforms. Our work will deliver new knowledge and yield much needed clarity to our understanding of the biologically important and cancer-related H2A.Z variant.