Time to part: how to produce sex cells with the right number of chromosomes

During meiosis, molecular ropes (red) pull chromosomes (blue) apart (top panels)
During meiosis, molecular ropes (red) pull chromosomes (blue) apart (top panels). But when the coiled complex of DNA and histone proteins doesn’t acquire a third chemical group at a specific spot, chromosomes do not separate successfully (bottom panels). Image credits: Tahsin Kuzdere

FMI researchers have honed in on a key process that happens when yeast cells divide to form gametes, which are the equivalents of human sperm and egg. Their work suggests that proteins conserved from yeast to humans ensure the production of gametes with the right number of chromosomes — a finding that may help to understand conditions such as Down syndrome and certain cancers.

To reproduce, most organisms create specialized sex cells called gametes. These cells must contain half the usual number of chromosomes so that when pairs of gametes merge, they can create new individuals with a complete genome. Precursor cells divide to form gametes in a process called meiosis, during which chromosomes separate. For this to happen successfully, the sections of DNA near the ends and centers of chromosomes must stay tightly spooled around histone proteins.

A hallmark of this tightly packed form of DNA are methyl groups on histones at a particular spot called H3K9. But the exact role of H3K9 methylation during the formation of sex cells is unclear. Working in fission yeast (Schizosaccharomyces pombe), researchers in the Bühler lab mapped H3K9 methylation across the whole genome during meiosis. They found that when cells start meiosis, the coiled complex of DNA and histones — which typically has two methyl groups at H3K9 — acquires a third methyl group at that spot. Cells that fail to get the third methyl group at H3K9 show chromosome segregation defects and produce gametes that are poorly viable.

Further experiments showed that a protein that is conserved from yeast to humans modulates the activity of the enzyme that is responsible for the switch in H3K9 methylation. Since this enzyme also has a counterpart in mammals, a similar process may occur during meiosis in humans. If so, the findings could help to understand conditions associated with abnormal chromosome segregation, including Down syndrome and some types of cancer.

Tahsin Kuzdere, Valentin B. Flury, Thomas Schalch, Vytautas Iesmantavicius, Daniel Hess, Marc Buehler Differential phosphorylation of Clr4SUV39H by Cdk1 accompanies a histone H3 methylation switch that is essential for gametogenesis EMBO Reports (2022) e55928

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