Homing in on developmental epigenetics

August 23, 2013, RIKEN
Figure 1: Fluorescent mouse primordial germ cells approximately 12 days after fertilization. Credit: 2013 Kuniya Abe, RIKEN BioResource Center

Germ cells have unique molecular features that enable them to perform the important task of transmitting genetic information to the next generation. During development from their embryonic primordial state, germ cells are thought to be reprogrammed by epigenetic modification of their DNA. However, due to the significant technical challenges associated with epigenetic analysis of rare cells such as primordial germ cells, the exact nature and effect of such epigenetic changes remains poorly understood. Kuniya Abe, Rieko Ikeda and colleagues from the RIKEN BioResource Center have now developed a method that enables as few as 100 cells to be analyzed for epigenetic changes, providing new insight into these processes.

Epigenetic changes regulate gene expression without altering the underlying DNA sequence. They involve highly specific chemical modifications of DNA and DNA-bound proteins that activate or deactivate individual or related sets of genes. DNA methylation is one such epigenetic mechanism, and the technique developed by Abe's team is an adaptation of an existing microarray-based assay method for detecting DNA methylation. "Our modification of the state-of-the-art approach might be useful for basic research as well as diagnostic applications when less than a nanogram of genomic DNA is available," says Abe.

Using their technique on embryonic , the researchers compared the extent to which the genomic DNA of , stem cells, and both male and female germ cells at different stages of development is tagged with methyl groups. Looking specifically at germ cells (Fig. 1), they found that large stretches of DNA on the X chromosome of male germ cells were depleted of methyl groups. These large 'hypomethylated' domains frequently included genes with germ cell- or testis-specific expression, including cancer testis antigen (CTA) genes, which are expressed in male germ cells and , but not in normal somatic cells. Genes in these regions were also expressed despite the presence of a histone modification that normally suppresses gene expression.

"The mechanistic basis for the relationship between hypomethylation and the expression of CTA genes remains to be established," says Abe. "We suspect that a change in nuclear architecture that controls the accessibility of the genes to the transcriptional apparatus might be involved."

Abe also notes that if CTA gene expression does indeed contribute to oncogenesis, then understanding the epigenetic regulation of these genes in germ cells could provide insight into the molecular events that cause certain types of cancer.

Explore further: Epigenetic changes to fat cells following exercise

More information: Ikeda, R., et al. Large, male germ cell-specific hypomethylated DNA domains with unique genomic and epigenomic features on the mouse X chromosome, DNA Research, 15 July 2013. dx.doi.org/10.1093/dnares/dst030

Related Stories

Epigenetic changes to fat cells following exercise

July 3, 2013
Exercise, even in small doses, changes the expression of our innate DNA. New research from Lund University in Sweden has described for the first time what happens on an epigenetic level in fat cells when we undertake physical ...

Scientists uncover mechanism by which plants inherit epigenetic modifications

September 20, 2012
During embryonic development in humans and other mammals, sperm and egg cells are essentially wiped clean of chemical modifications to DNA called epigenetic marks. They are then held in reserve to await fertilization.

The secret of DNA methylation

June 18, 2013
Methylation refers to a chemical modification of DNA and this modification can occur in millions of positions in the DNA sequence. Until now, scientists believed that this epigenetic phenomenon actively reduced the expression ...

Recommended for you

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

Can mice really mirror humans when it comes to cancer?

January 18, 2018
A new Michigan State University study is helping to answer a pressing question among scientists of just how close mice are to people when it comes to researching cancer.

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.