A mechanism of histone exchange involved in heterochromatin

Mobility of transposons, discovered by Barbara McClintock in the middle of the 20 th century, poses a threat to genome integrity. However, most transposons are silenced and enriched in specific regions of the genome called heterochromatin. If this silencing mechanism is lost, transposons can be mobilized, with deleterious consequences, as shown in tumor formation. Maintenance of heterochromatin is relatively well investigated, but how silencing by heterochromatin is initiated in the first place is poorly understood and the main question of the project. The lab of Dr. Frederic Berger, who will host the proposed work, discovered that heterochromatin predominantly contains a distinct variant of histone H2A, one of the four histone types that constitute the building blocks of chromatin. It is hypothesized that the dynamic deposition of the specific variant, called H2A.W, is responsible for establishing heterochromatin in plants. The aim of the project is to characterize the biochemical properties of the mechanism involved in H2A.W deposition. This involves an uncharacterized protein belonging to a large class of chromatin remodelers. Studying the biochemical action of remodelers is a burgeoning field of chromatin biology. The main applicant of this proposal, Dr. Akihisa Osakabe, will provide his special expertise in chromatin biochemistry required to tackle this problem at the Vienna Biocenter. Complementary strategies will be combined to understand the properties of the H2A.W remodeler and to define its function in the establishment of heterochromatin. As a similar type of remodeler is present in animals, the findings will have a wide impact on understanding heterochromatin establishment in a broad range of species including humans and mechanisms of chromatin-related diseases.

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