Prior to cell division, chromosomes are seemingly a jumbled mess. During cell division, parent cell chromosomes and their duplicates sort themselves out by condensing, becoming thousands of times more compact than at any other time. Researchers have long assumed that genes become “silent” during cell division, not being transcribed into proteins or regulatory molecules. This has left open the question of how genes get properly re-activated after cell division. Now, researchers in the Perelman School of Medicine at the University Pennsylvania have found that gene expression actually continues during cell replication. Their findings are published this week in Science.
Although chromosomes are extremely compact during cell division, with sequences for regulatory molecules buried and previously presumed to be unavailable to be transcribed, Palozola found that most genes and their nearby regions that promote gene function are still actively expressed. She discovered how cells wake up after cell division and recall “who they are.” What ultimately drives cell differentiation are sequences of enhancer molecules located away from the gene they act on.
The laboratory of Gerd Blobel at the Children’s Hospital of Philadelphia had previously shown that these far-away modifiers “nap” during division, since it only lasts about 30 minutes — relatively quickly in biological terms — and come back online after a cell division cycle is complete.
“The most amazing thing about this study is that in the end, we had to throw what we thought we knew about this basic aspect of gene regulation out the window,” Zaret said. “The findings indicate that we need to think about how promoters, rather than enhancers, are regulated during cell division. This refocusing will tell us how a cell’s identity, as defined by the genes it expresses, is retained through cell division. We hope it will improve our ability to deliberately change a cell’s identity to create new cells and tissues for therapeutics and research.” Paper. (paywall) – Katherine C. Palozola, Greg Donahue, Hong Liu, Gregory R. Grant, Justin S. Becker, Allison Cote, Hongtao Yu, Arjun Raj, Kenneth S. Zaret. Mitotic transcription and waves of gene reactivation during mitotic exit. Science, 2017; eaal4671 DOI: 10.1126/science.aal4671 More.
When we see the complexity, it’s amazing that things go wrong only as often as they do.
See also: Origin of mitochondria a “unique and hard” evolutionary problem