Earnshaw lab paper featured in the Journal of Cell Science. Authors Image Mitotic cell with aligned chromosomes at metaphase. DNA, blue; Microtubules, red; HAC, green; H3-ser10 phosphorylation white. Image by Nuno Martins. Martins, N.M.C., Cisneros-Soberanis, F., Pesenti, E., Kochanova, N.Y., Shang, W.H., Hori, T., Nagase, T., Kimura, H., Larionov, V., Masumoto, H., Fukagawa, T., and Earnshaw, W.C. Summary of by Lori Koch Every chromosome in a cell has a region known as the centromere which ensures it is inherited. Centromeres are defined by the presence of specialised proteins, most importantly CENP-A, which forms the basis of the kinetochore complex that connects the chromosome to the spindle fibres that direct it into the daughter cells during cell division. In human cells, the DNA surrounding the centromeres is heterochromatic, carrying specialized chemical signatures such as methylation on histone H3 at lysine 9 (abbreviated H3K9me3). Whether the surrounding H3K9me3 is required for maintenance of CENP-A at the centromere was unclear from previous studies due to seemingly contradictory observations. In their recent investigation published in the Journal of Cell Science, Earnshaw Lab researchers used cells carrying a non-essential synthetic human artificial chromosome to investigate centromere maintenance in human cells without disrupting native chromosomes. They engineered cells to tether the demethylase JMJD2D specifically to the centromere of the artificial chromosome. Addition of a drug to the growth media caused the demethylase to fall off of the chromosome. JMJD2D tethering caused a reduction in H3K9me3 surrounding the centromere and after 8 days, they found that CENP-A levels were reduced and chromosome segregation errors increased. Their most important finding was that when the drug was added and JMJD2D fell off of the chromosome, the heterochromatin gradually returned to its original level and the centromere recovered its function. Thus, this study discovered the first evidence for a homeostatic control of heterochromatin levels at centromeres that is important for chromosome segregation. Related links Journal Link Earnshaw Lab Website DOI This article was published on 2024-06-17
