Homing in on developmental epigenetics

August 23, 2013
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

A rogue gene is causing seizures in babies—here's how scientists wants to stop it

July 26, 2017
Two rare diseases caused by a malfunctioning gene that triggers seizures or involuntary movements in children as early as a few days old have left scientists searching for answers and better treatment options.

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

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.