DNA packaging shifts suddenly during cell division
The DNA inside a cell is not always equally tightly or loosely packed. New research shows that this packaging structure moves far more during cell division than previously thought, and that most of the change happens at one very specific moment.
DNA in a cell nucleus is not randomly coiled. It is organized into two zones: active regions where genes are read (A compartments) and inactive regions that are kept closed off (B compartments). Together these determine which genes are switched on and which are not. Until now, this organization was thought to remain fairly stable throughout cell division, with the exception of the moment the cell actually splits in two.
The researchers, publishing in eLife, developed a method to measure chromatin structure at specific moments during the cell cycle without using chemical agents that disrupt the cell. They combined a genetic indicator of cell cycle stage with a technique that maps the spatial organization of the entire genome (Hi-C), working in mouse embryonic stem cells.
An unexpected shift at the start of S phase
What they found was surprising. The strength of the A/B compartment organization increased sharply at the transition from G1 phase to S phase, the point at which the cell begins copying its DNA. This strengthening, which they called chromatin maturation, did not depend on the actual copying process: even when DNA synthesis was blocked, the reorganization still occurred. They describe four distinct stages in chromatin dynamics: unfolding, maturation, stabilization, and refolding.
For longevity research, this mechanism is relevant for an indirect reason. Chromatin organization changes with aging: genes that should be silent become active, and vice versa. Understanding how that organization normally works and is regulated is a prerequisite for understanding how it goes wrong during aging. The study involves mouse models and fundamental cell biology; direct conclusions for human aging cannot yet be drawn.
Cell division as a window into gene regulation
The finding that the G1/S transition is a critical moment for genome reorganization also has implications for cancer research. Cancer cells often divide rapidly and abnormally: disruptions in chromatin structure at that transition may contribute to aberrant gene expression. The research adds a new layer of detail to our understanding of how cells regulate their DNA during division.
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