Author: Tina Hesman Saey / Source: Science News
MARKING THE SPOTS
Turning on genes may work like forming a flash mob.
Inside a cell’s nucleus, fast-moving groups of floppy proteins crowd together around gene control switches and coalesce into droplets to turn on genes, Ibrahim Cissé of MIT and colleagues report June 21 in two papers in Science.
Researchers have previously demonstrated that proteins form such droplets in the cytoplasm, the cell’s jellylike guts. Some, including Cissé’s MIT colleagues Richard Young and Phillip Sharp, have proposed that this process — called phase separation — could also happen in the nucleus when cellular machinery turns genes on, which involves copying DNA instructions into RNA messages.
If confirmed, the discovery challenges earlier ideas that gene activity is controlled by single molecules of stable protein complexes that remain stuck to DNA for long periods.
Cissé and colleagues used super-resolution microscopy to view single molecules of protein in live mouse embryonic stem cells. In particular, they were interested in RNA polymerase II, an enzyme that copies DNA into RNA, and parts of the Mediator complex, a group of proteins that help kick-start that copying process, called transcription. The researchers tagged the proteins with a fluorescent protein and watched what happened.
RNA polymerases II and Mediator proteins each formed large clusters, each with about 200 to 400 molecules. Those clusters had properties of phase-separated droplets: Each cluster formed distinct dots when viewed through the microscope. Those dots could fuse together, like oil droplets merging in water. And the droplets could be dispersed with alcohol. That’s convincing evidence that Cissé sees phase-separated condensates, says Anthony Hyman, a biologist at the Max…
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