DNA tags mostly deleted in human germ cells

The few epigenetic markers that escape erasure might pass on risk for some diseases

embryo

EARLY ERASER  Sometime in the first trimester, human embryos’ reproductive cells get wiped mostly clean of chemical tags marking the DNA.

Andrzej Zachwieja and Jan Walczewski/Wikimedia Commons (CC BY-SA 3.0)

Mom and dad’s lifestyle may leave less of a mark on future generations than scientists have suspected.

In the first weeks after conception, some of the cells in human embryos get their genetic blueprints scrubbed clean, conclude three new studies published June 4 in Cell. Those cells, the ones that become sperm or eggs, could beget the tiny embryos’ future offspring.

The genetic scrub-down erases notes that environmental factors write on parents’ DNA, so that a child’s sperm or eggs start off with a clean slate — mostly. One study revealed that a few spots in the genome, the complete set of DNA blueprints, avoided the cleanse. So a few of the DNA notes that people rack up during their lives could potentially pass from generation to generation, possibly transmitting risk for diseases such as schizophrenia far down the family tree.

“But by and large, this paper says that’s very unlikely to happen,” says epigeneticist Rob Martienssen of Cold Spring Harbor Laboratory in New York. That’s because nearly all of the notes are erased, he says.

In the last two decades or so, scientists have begun to understand how these notes work. A collection of chemical, or epigenetic, tags decorates DNA, and like pencil notes scrawled atop blueprints, these tags carry extra information. They modify a cell’s building plans — by telling which genes to switch on or off — without actually changing the DNA blueprints.

What people eat, what they breathe and how much they exercise can all influence their particular assortment of chemical tags, such as methyl groups that attach to some DNA locations.

Some scientists have suggested that these methyl tags might be inherited, just as genes pass from parent to child to grandchild and so on. Researchers have shown that babies born to obese fathers carry a different set of tags than kids of normal-weight dads. Prenatal exposure to smoking seems to alter babies’ set of tags, too.

But the evidence that parents’ lifestyle affects more than the following generation or two is still fuzzy, says study coauthor Azim Surani, a developmental epigeneticist at the University of Cambridge.

And the idea that people pass down epigenetic information for multiple generations doesn’t completely jibe with what scientists have learned from mouse studies. In mice, germ cells, which give rise to sperm and eggs, undergo a thorough cleaning: The chemical tags marking DNA get erased.

“That should theoretically remove any signals that are acquired during the lifetime,” Martienssen says.

But until now, no one had worked out what happened in human germ cells. So Surani and two other research groups separated the germ cells from the other cells that make up 4- to 19-week-old human embryos. Then the teams mapped out the germ cells’ DNA tags, as well as the genes at work.

As in mice, the chemical tags on human germ cells’ DNA mostly got swept away. And compared with other cells in the human embryo, the germ cells endured a heavy-duty wipe-down.

“It’s quite an amazing erasure process,” Surani says. Of the tags his team studied, only about 4 percent stuck around, compared with some 37 percent in a different kind of embryonic cell.

The results suggest that germ cells have developed a strong system for ensuring that epigenetic information doesn’t sneak through to subsequent generations. Still, not every tag was erased. And of the remaining tags, some marked spots in the genome linked to schizophrenia, obesity and multiple sclerosis.

“It’s potentially provocative,” says Wolf Reik, an epigeneticist at the Babraham Institute in Cambridge, England. Because the erasure is not complete, there’s still a chance that DNA tags could travel down multiple generations, he says.

Surani agrees. “I don’t want to be dogmatic and to say it never happens,” he says. “But look at the data. The bulk of the epigenetic information gets erased.”

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