OCT 03, 2016 12:04 PM PDT

Genomic Imprinting Does not Stay Stable Over Time

WRITTEN BY: Carmen Leitch
To put it simply, organisms inherit a copy of each gene from each parent. For a small group of genes, roughly one hundred, a copy from the father or the copy from the mother is the only one expressed. The other copy is not used, and is silenced in a phenomenon known as genomic imprinting. That silencing was considered to remain stable over the life of the organism. New work done in the mouse and published in Cell Reports has shown however, that such genomic imprinting does not always last in some types of cells. The short video below discusses genomic imprinting in more depth with Dr. Gudrun Moore, who studies epigenetics.
 


Researchers working at the Whitehead Institute used a recently published technology that analyzed alterations in epigenetic markers on DNA over a period of time. This reporting tool enabled them to observe a particular imprinted methylation mark that must be put onto either the maternal or paternal copy of DNA, or cell death will result, in mouse embryonic stem cells. Researchers investigating these features sometimes refer to intergenic differentially methylated regions or IG-DMR.

Mice that carried the reporting technology in their genome were then observed as they grew into adulthood. The researchers saw that the imprinted methylation marks actually began to show variance from one cell to another. This variation also changed depending on the type of cell. For example, while retina cells maintained a lot of their genomic imprinting, cells of the intestine did not keep it.

The report indicated that epigenetic marks could be controlled and regulated in adult tissues. It’s a challenge to the idea that genomic imprinting is static over time and is continuously maintained in the same state. The study indicated that while one set of parental genes likely must be silenced for proper development, that silencing begins to change in various types of cells. In cells where the epigenetic silencing marks are lost, the genes can then cause gene expression, or can halt gene expression.
The graphical abstract from Cell Stelzer et al

"There seems to be a requirement for more fine-tuned gene expression of imprinting in different tissues throughout development and in adulthood, which is a very exciting idea," explained the study first author, Yonatan Stelzer, a postdoctoral fellow in the lab of senior author Rudolf Jaenisch of the Whitehead Institute for Biomedical Research and MIT.

In the future the investigators would like to determine why differences in genomic imprinting occur in various cell types over time, as well as what the functional consequences to changes in imprinting might be. Another question to study is whether environmental factors can influence the regulation of these changes.

"It's essentially the first time that we can see epigenetic changes during development in vivo, this opens up a lot of questions because DNA methylation plays a role in key processes that we did not have a readout for," Stelzer said. "Now we can start applying unbiased screens of small molecules to affect this epigenetic phenomenon and ask basic questions on the role of DNA methylation changes in early development and disease."
 


If you would like to know more about genomic imprinting, the recent lecture above dealing with the subject is from the National Institutes of Health.

Sources: Eurekalert! via Cell PressCell
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