Epigenetic inheritance: establishment and transmission of specialised chromatin domains

DNA is a tape that carries the instructions for building all cell types in our bodies. DNA is packaged in the cell nucleus by wrapping it around spools made of histone proteins to make chromosomes. CENP-A is an exclusive histone that forms spools at one region of each chromosome – the centromere. These CENP-A spools programme construction of protein machines that ensure equal segregation of duplicated chromosomes into daughter cells during cell division.

We aim to decipher the instructions that result in CENP-A spools being placed on chromosomes. Heterochromatin is a structure formed when ordinary histone spools are clamped shut by chemical modifications. Heterochromatin near centromeres aids the placement of CENP-A spools. We will determine how heterochromatin is positioned at the edge of the nucleus and if this location is important for directing CENP-A placement. Heterochromatin at other places on chromosomes controls which instructions are read and may allow the formation of different cell types. We will determine if heterochromatin forms sporadically and its role in generating cells with distinct characteristics.

Understanding processes involved in constructing functional centromeres will provide important information about diseases including cancer.