Many animals, humans included, begin life as a single cell following the union of sperm and egg cells. As scientists seek to understand the earliest stages of life following that fusion of parent cells, they are beginning to shed light on the complex molecular changes that program our bodies’ growth and development.
|DNA from sperm, green, and egg, red, prepare for first cell division. (Image by Khursheed Iqbal)|
A joint team of researchers led by Piroska Szabo, Ph.D., assistant professor in the Department of Molecular and Cellular Biology, and Gerd Pfeifer, Ph.D., Lester M. and Irene C. Finkelstein Chair in Biology and chair of the Department of Cancer Biology, recently pulled back the curtain on a mysterious change that takes place in the first few hours after sperm and egg cells join.
In a study published in the March 1 issue of the Proceedings of the National Academy of Sciences, the scientists described how some DNA in the newly formed zygote — the cell formed by the fusion of sperm and egg — apparently is stripped of chemical caps called methyl groups.
Methyl groups help a cell control the activity of genes. To assure normal development, a cell must carefully control which genes are active and which are turned off at any particular time, so it adds or removes methyl groups at key points on the DNA (a process called methylation).
A zygote contains two copies of DNA — one from the father’s sperm cell and one from the mother’s egg. Scientists recently found that most of the sperm cell’s DNA loses its methyl groups shortly after the sperm enters the egg. The cause of this global demethylation was unclear; no enzyme was known that could remove the methyl groups.
In the current study, the City of Hope team discovered why no demethylating enzyme had been found: No such enzyme is involved in the process.
Instead, the zygote changes the sperm’s methylated DNA to a new form of DNA, called hydroxymethylated DNA, that went undetected in previous tests. The altered DNA unfurls and opens up, and key genes may be turned on.
“This conversion of methylated DNA happens within hours of the zygote’s formation,” said Szabo.
According to Pfeifer, the change is one of the first crucial steps in the organism’s growth.
“It is a key step in reprogramming the zygote’s DNA, which is critical for turning on genes that drive mammalian development,” he said.
The researchers now are working to confirm which enzymes convert methylated sperm DNA to its new form.
Additional authors on the study include postdoctoral fellows Khursheed Iqbal, Ph.D., and Seung-Gi Jin, Ph.D. The study was supported by the National Institutes of Health.