Creation and function of neighborhoods in eukaryotic chromosomes: regulation by SWR1-Com, a desposition complex for histone variant H2A.Z

Chromatin is the complex of DNA and protein material that make up chromosomes, home to the genetic code. The basic unit of chromatin is the nucleosome, a fundamental building block consisting of DNA wrapped around an octamer of histone proteins. A large number of proteins involved in cancer development and the genetic susceptibility to devastating diseases such as Ataxia Telangiectasia (a progressive immunological and neurological disorder) act through modification of chromatin structures and interfere with normal chromatin function. Differences in chromatin structures between adjacent regions specify the properties of larger macrodomains called neighbourhoods. The shape and structure of these neighbourhoods influence chromosome behavior, while complex regulatory mechanisms that ultimately involve chromatin ensure that each cell expresses only the appropriate genes, duplicates its genome with high fidelity, divides only when required, all while combating constant assaults on its DNA. Failure in any of the mechanisms regulating these events can lead to disease. These chromatin structures themselves can also be inherited, creating an additional complex set of influences that are crucial for the identity and activity of the cell. The molecular biology of chromatin structures and their role in chromosome biology and genome function in health and disease is the focus of Michael Kobor’s research. Specifically, he is studying a unique chromosomal neighbourhood containing a specialized histone variant known as H2A.Z, which is deposited into chromatin by a large protein complex. Using innovative genome-wide approaches, Dr. Kobor’s team aims to uncover the rules and principles of histone variant function.