SCIENCE: Salk scientists discover biological trigger that starts the day


Salk Institute scientists have found a new control governing the biological clock governing the sleep cycle of animals from mice to fruit flies ---- and presumably including humans.

The controller is an enzyme called JARID1A. This enzyme is well-known in biology for its role in modifying histones, proteins that wrap DNA in a protective complex called chromatin.

Unexpectedly, the scientific team discovered that the enzyme also starts the daily wake-up process.

Moreover, they found that depleting this enzyme disrupts the sleep cycle of flies and mice, producing irregular periods of sleep and wakefulness.

New therapies to restore normal sleep patterns in those suffering from sleep disorders may be possible by targeting this process with drugs, said Luciano DiTacchio, a Salk researcher who led the study with  colleague Satchidananda Panda, the lead author on the study.

The study was published last week as an article in the journal Science.

Circadian clocks, as these mechanisms are known, evolved hundreds of millions of years ago to help control the sleep and activity patterns of organisms.

Their basic patterns are the same in organisms greatly differing from human beings, which makes research in fruit flies and mice pertinent to human biology, DiTacchio said.

"They're oscillations in a lot of things, from behavior to physiology," DiTacchio said. "If you look at anything we do, humans, mice, flies, plants, even ---- we follow patterns. Since we live on a planet that has light and dark cycles, we evolved in an environment that has changes in temperature and other things. Pretty much every organism has a timing mechanism. This mechanism is present in every cell of your body."

Genes governing this process form what's called a "genetic circuit," DiTacchio said.

That means genes trigger sequences of events that precede and follow each other in a characteristic circular pattern.

However, the initial trigger that starts the day wasn't known. JARID1A plays that role, closing this gap in understanding how this circuit works.

The study article said JARID1A plays a "nonredundant role" in circadian oscillation, another way of saying that the enzyme's role is essential and not duplicated by other molecules, DiTacchio said.

"It's kind of like a switch, if you will," DiTacchio said.

People with disrupted circadian cycles, such as those who work odd shifts, are at risk for several kinds of diseases.

"They gain weight more, there's an increase in certain cancers, and there are implications that disrupting the circadian cycle has a detrimental effect on your body," DiTacchio said.


