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When sperm meets egg, the chemical instructions on sperm cells must be erased so that human life can start anew.
One way these instructions are erased is through demethylation, the removal of the chemical tags known as methyl groups that dot the underlying DNA of cells. Though scientists have known about this phenomenon for a decade, they have not understood how such “reprogramming” occurs.
Now, a study from the University of North Carolina at Chapel Hill, School of Medicine, has illuminated a key step of demethylation giving stem cell researchers critical information as they attempt to reprogram adult cells to become stem cells.
Previous research had identified how methyl tags on sperm DNA are converted to hydroxymethyl, before disappearing completely. The current research, published online in the Sept. 22, 2011, issue of Science (ScienceExpress), suggests that the disappearance of these chemical tags in not an active process catalyzed by an enzyme but is rather a passive process.
“The biological function of this molecular event is not known yet, we are still trying to figure it out,” said senior study author Yi Zhang, PhD, Kenan distinguished professor of biochemistry and biophysics at UNC and an investigator of the Howard Hughes Medical Institute.
“But we do believe it must be important for development, because it happens before the cells committed to any specific cell types.” Zhang is also a member of the UNC Lineberger Comprehensive Cancer Center.
Zhang’s postdoctoral fellow and co-author Azusa Inoue, PhD, developed a technique that enabled him to visualize chromosomes the threadlike bodies that contain the cell’s DNA at the earliest stage of life.
Through a high resolution staining technique, he was able to compare the levels of methyl tags and hydroxymethyl tags in sperm and egg chromosomes in the first developmental stages of life.
Their findings confirmed what they already knew that sperm DNA goes through a chemical conversion from methyl to hydroxylmethyl while the egg DNA does not.
But it also found something new that the hydroxymethyl tags disappeared over time, passively through dilution, as the DNA divided and the newly formed embryo doubled from first one-cell, then to two- and four-cells.
The clinical implications are still not clear, Zhang says, as researchers still don’t know why male DNA undergoes such a conversion when female DNA does not.
It may have something to do with difference between the chromatin protein structure that packages the DNA of the sperm and of the egg. Zhang and others in the field are actively pursuing this possibility.
The research was funded by the Howard Hughes Medical Institute and the National Institutes of Health.
Original article: http://news.unchealthcare.org/news/2011/september/unc-researchers-identify-important-step-in-sperm-reprogramming