Dynamics of DNA packaging helps regulate formation of heart

ScienceDaily (Sep. 27, 2012) A new regulator for heart formation has been discovered by studying how embryonic stem cells adjust the packaging of their DNA. This approach to finding genetic regulators, the scientists say, may have the power to provide insight into the development of any tissue in the body -- liver, brain, blood and so on.

A stem cell has the potential to become any type of cell. Once the choice is made, the cell and other stem cells committed to the same fate divide to form organ tissue.

A University of Washington-led research team was particularly interested in how stem cells turn into heart muscle cells to further research on repairing damaged hearts through tissue regeneration. The leaders of the project were Dr. Charles Murry, a cardiac pathologist and stem cell biologist; Dr. Randall Moon, who studies the control of embryonic development, and Dr. John Stamatoyannopoulos, who explores the operating systems of the human genome.

The paper's lead author is Dr. Sharon Paige, a UW MD-PhD student who completed her Ph.D. in Dr. Murry's lab.

The results are published in the Sept. 28 edition of Cell.

Paige, an aspiring pediatric cardiologist, said, "By identifying regulators of cardiac development, this work has the potential to lead to a better understanding of the causes of congenital heart disease, thereby paving the way for therapeutic advances."

Previously UW researchers had examined the signals that prod cells to grow into various kinds of heart tissue. In this case, the researchers entered a relatively unexplored area. They decided to look at the genetic controls behind the transformation of stem cells into heart tissue.

Because stem cells keep their DNA code under wraps until needed, the scientists examined how this packaging is altered over time to permit reading of portions of the code and thereby produce changes in the cell.

DNA is wound up into a structure called chromatin. "DNA can be packaged as tightly closed, neutral or activated," Murry explained. The tightly closed state, he said, is analogous to setting the brakes on a car.

Like a child who clams up when asked, "What will you be when you grow up?" stem cells are protective of the genes that will determine their future cell type, or what scientists call their cell fate.

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Dynamics of DNA packaging helps regulate formation of heart