Shutting down of DNA stretches, not single genes, causes cells to mature

London, Jan 19 (ANI): Johns Hopkins researchers have found that the silencing of large DNA stretches and not single genes is what causes the gradual maturing of embryonic cells into cells as varied as brain, liver and immune system cells,

In the study on mouse brain and liver cells, as well as embryonic stem cells, led by Johns Hopkins University School of Medicine professor Andrew Feinberg, M.D., M.P.H., the researchers focussed on a kind of epigenetic modification to histones, the molecular "spools" that DNA winds around in the cell nucleus.

The modification is a variety of the so-called epigenetic changes that alter the function of cells without directly altering the nuclear DNA in the cells.

In earlier studies, scientists had found that histone modifications appear to silence individual genes in the DNA that coils around affected histones.

However, when the researchers compared the activity of thousands of genes in the liver and brain cells, they found that a particular modification - in which two methyl groups clip onto histones - seemed to silence long stretches of DNA containing many genes at once.

The silenced stretches varied greatly between the different types of cells.

Thus, the researchers wondered if these sections - called large organized chromatin K9 modifications, or LOCKS - might be responsible for the transition from the "blank slate" quality of embryonic cells to the specialized functions that mature cells take on.

To unravel the mystery, scientists looked for LOCKs in mouse embryonic stem cells. Unlike mature, adult liver and brain cells, in which about 40 percent of the genome was silenced by LOCKs, the embryonic stem cells had no LOCKs.

Then, the researchers compared the regions of DNA affected by LOCKs between mouse liver and brain cells and their corresponding human cells.

It was found that the same cell types in both organisms had remarkably similar regions of DNA silenced by LOCKs.

Thus, the researchers suggested that the same genes necessary to control cell function are affected in mice and people.

"These results suggest that LOCKs appear gradually during development, refining cells' functions as they differentiate into particular cell types. Our experiments suggest that the whole forest of genes is changing, but people have been looking at the individual trees," Nature quoted Wen as saying.

The findings were published in Nature Genetics online. (ANI)