Express yourself: How zygotes sort out imprinted genes

Feb 16, 2012

Writing in the February 17, 2012 issue of the journal Cell, researchers at the Ludwig Institute for Cancer Research, the University of California, San Diego School of Medicine and the Toronto Western Research Institute peel away some of the enduring mystery of how zygotes or fertilized eggs determine which copies of parental genes will be used or ignored.

In developing humans and other , not all genes are created equal – or equally used. The expression of certain genes, known as , is determined by just one copy of the parents' genetic contribution. In humans, there are at least 80 known imprinted genes. If a copy of an imprinted gene fails to function correctly – or if both copies are expressed – the result can be a variety of heritable conditions, such as Prader-Willi and Angelman syndromes, or diseases like cancer.

In the Cell paper, a team of scientists, led by Bing Ren, PhD, head of the Laboratory of Gene Regulation at the Ludwig Institute for at UC San Diego, describe in greater detail how differential DNA methylation in the two parental genomes set the stage for selective expression of imprinted genes in the mouse. Differential DNA methylation is essential to normal development in humans and other higher organisms. It involves the addition of hydrocarbon compounds called methyls to cytosine, one of the four bases or building blocks of DNA. Such addition alters the expression of different genes, boosting or suppressing them to help direct embryonic growth and development.

The process is sometimes called epigenetic regulation. Epigenetics is the study of factors influencing inheritance beyond the genes themselves. "DNA is just half the story," said Ren, who also heads the San Diego Epigenome Center, one of four centers established by the National Institutes of Health to focus on epigenetics research.

"Understanding how these limited imprinted regions control regulation can help us better understand how certain diseases happen," said Ren, a professor of cellular and molecular medicine in the UC San Diego School of Medicine. "That can help us develop better diagnostic tools for detecting genetic abnormalities and perhaps learn how to predict whether something bad will happen."

Using a deep sequencing, high-throughput screening technology developed by Joseph Ecker at the Salk Institute for Biological Studies, Ren and colleagues found parent-of-origin specific DNA methylation imprints at 1,952 dinucleotide sequences in the mouse genome. The imprinted sequences formed 55 discrete clusters that included virtually all of the known germline differentially methylated regions and 23 previously unknown regions.

"That suggests it's a very accurate tool," said Wei Xie, first author of the paper and a postdoctoral researcher in Ren's laboratory.

The researchers also found a unique type of methylation in the brain that was previously only seen in embryonic cells. "At this point we do not know what the significance of this modification is in the brain, but it is very specific, suggesting that it correlates to an important biological function" said Cathy L. Barr, PhD, a senior scientist at the Toronto Western Research Institute, the Hospital for Sick Children and co-author of the paper.

Explore further: Scientists find key to te first cell differentiation in mammals

add to favorites email to friend print save as pdf

Related Stories

Epigenetic signals differ across alleles

Feb 12, 2010

Researchers from the Institute of Psychiatry (IoP), King's College London, have identified numerous novel regions of the genome where the chemical modifications involved in controlling gene expression are influenced by either ...

Recommended for you

Research helps identify memory molecules

12 hours ago

A newly discovered method of identifying the creation of proteins in the body could lead to new insights into how learning and memories are impaired in Alzheimer's disease.

Computer simulations visualize ion flux

13 hours ago

Ion channels are involved in many physiological and pathophysiological processes throughout the human body. A young team of researchers led by pharmacologist Anna Stary-Weinzinger from the Department of Pharmacology ...

Neutron diffraction sheds light on photosynthesis

13 hours ago

Scientists from ILL and CEA-Grenoble have improved our understanding of the way plants evolved to take advantage of sunlight. Using cold neutron diffraction, they analysed the structure of thylakoid lipids found in plant ...

DNA may have had humble beginnings as nutrient carrier

Sep 01, 2014

New research intriguingly suggests that DNA, the genetic information carrier for humans and other complex life, might have had a rather humbler origin. In some microbes, a study shows, DNA pulls double duty ...

Central biobank for drug research

Sep 01, 2014

For the development of new drugs it is crucial to work with stem cells, as these allow scientists to study the effects of new active pharmaceutical ingredients. But it has always been difficult to derive ...

User comments : 0