A team of researchers from the MRC Human Genetics Unit is using neo-centromeres as a model system to gain insights into the properties of canonical centromeres. The cells in our body are constantly dividing to produce more cells that are genetically identical to them - a process called mitosis. During this process, the DNA of the cell nucleus is split into two equal sets of chromosomes. This usually happens in a carefully organised sequence of steps, as unequal division of DNA between cells can lead to genetic instability and cause diseases such as cancer. As cells prepare to divide, chromosomes are replicated to form two "daughter strands" called sister chromatids. These are held together by a structure called centromeres. Centromeres are highly specialised DNA sequences that play an important role in the separation of sister chromatids. The centromere is necessary to maintain the stability of the genome during cell division, but it is still not clear how it works. Due to the repetitive nature of human centromeres it has been impossible to characterise their chromatin structure. In our study we get around this by taking advantage of the properties of neocentromeres to develop a model system which we used to analyse centromeric chromatin. This understanding of centromere chromatin structure paves the way for important further studies on centromere function, kinetochore assembly and chromosome evolution. Dr Catherine Naughton Senior Postdoctoral Scientist, MRC Human Genetics Unit Researchers have developed a model system using neo-centromeres to study centromeres Studying centromeres has been challenging because they contain special regions of repetitive DNA sequences that are very difficult to read and edit compared to DNA outside the centromere. To solve this problem, Naughton and colleagues have developed a model system using neo-centromeres. Neocentromeres are new centromeres that form on a chromosome in a region that is not normally centromeric. Although they are functionally and structurally similar to normal centromeres, they do not contain repeating sequences. This makes them a powerful tool for studying centromeric chromatin structure. The researchers show that the chromatin structure at the centromere has an "open" configuration, which is probably important for the functioning of the centromere. They also show that the process of transcription is necessary to achieve the open structure. They hypothesise that the remodelling of chromatin fibres provides a suitable environment for proteins that must bind to the centromere during mitosis. In contrast, they found that the surrounding chromatin regions were remodelled into a compact structure, and suggest that this serves to provide structural rigidity. These results shed light on the properties of normal centromeres. Related Links MRC Human Genetics Unit Nick Gilbert Research Group Catherine Naughton profile "Human centromere repositioning activates transcription and opens chromatin fibre structure" publication This article was published on 2022-11-03
