Chromosomes reconfigure as cell division ends

Chromosomes reconfigure as cell division ends

Cellular senescence -- when a cell can no longer divide -- is a programmed stage in a cell's life cycle. Sometimes, as in aging, we wish it didn't happen so much and sometimes, as in cancer, we wish it would happen more. Given its important impacts on health, biologists wish they could explain more about what's happening in cells when senescence takes hold. A new study helps by showing that chromosomes become somewhat transformed, altering their patterns of gene expression.

Overall, the team found, chromosomes become much more compact, though some parts of them expand in volume. An analysis of their spatial organization finds that most genes move into areas called "B" compartments that are locked down by tightly wound chromatin that prevents their expression. Many, however, move into "A" compartments that are looser and therefore more open for gene expression.

The kinds of genes affected by these changes are often ones of relevance to senescence. In their analysis, for example, the scientists found that about one in eight genes associated with cell proliferation and other relevant cell functions switch from relatively loose A compartments to more restrictive B compartments.

The scientists saw that while the chromosomes' arms and the "telomeres" at their tips scrunched up, the relatively tiny middle -- the centromere -- expanded. Within the centromere certain areas of repetitive DNA called alpha satellites expanded dramatically and become expressed.

All of this information allowed them to create the first 3-D models of how chromosomes change in senescent cells.

Now the team is delving deeper into the compartment switches (between A and B) that change the regulation of genes in senescent vs. nonsenescent cells. They hope to understand and model those transitions and their consequences in greater detail.