The chromosomes of the body's mature cells are known to have long stretches of K27-tagged spools, where genes are off limits, and other regions where the spools are tagged on K4, allowing the cell to activate the local genes.
The Broad Institute scientists have made use of new techniques that let them visualize which spools along a chromosome carry the K27 or K4 tags.
They decided to map the tags in embryonic cells because of the interest of seeing how the process of determining cell fate is initiated.
In the current issue of Cell, a team led by Bradley Bernstein and Eric Lander reports that they looked at the chromatin covering the regions where the master regulator genes are sited.
They found to their surprise that these stretches of chromatin carried both kinds of tags, as if the underlying genes were being simultaneously silenced and readied for action.
These bivalent domains, as the biologists called the ambiguously tagged stretches of chromatin, were puzzling at first but make sense in terms of what embryonic cells are meant to do.
Each cell must avoid being committed to any particular fate for the time being, so all its master regulator genes must be repressed by tight winding of the spools that hold their DNA. But the cell must be ready at any moment to activate one specific master regulator as soon as its fate is determined.
The Broad team then looked at the chromatin state of the master regulator genes in several kinds of mature cell.
As was now predictable, they discovered that the bivalent domains had resolved into
carrying just one type of mark, mostly the K27 tag, indicating the master genes there were perman-ently repressed.
But in each kind of mature cell one or more of the domains had switched over to carrying just the K4 tags, within which genes would be active.
"We think the bivalent state is keeping the embryonic cells poised," Bernstein said. "It's very special; we didn't see it in any other kind of cell."
Bernstein's team worked with mouse cells, but its findings have been confirmed in human embryonic stem cells by Tong Ihn Lee and Richard Young of the
Whitehead Institute.
They and their colleagues started not with the bivalent domains but with the polycomb complex that gives the spools their K27 tag.
Working with human embryonic stem cells, the Lee-Young team mapped where a component of the polycomb complex was attached to the chromatin.
They found it had sought out some 200 sites where many of the master regulator genes of human cells are located. The Whitehead team's article, also published in the current Cell, indicates that in mice and people, just as in fruit flies, the same ancient mechanism is used to make the crucial decisions that determine cell fate.
"This is a very nice piece of work and will be widely interesting because it is funda-mental," said Allan Spradling, an expert on embryonic devel-opment at the Carnegie Institution of Washington, referring to both teams' findings.
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