How DNA is Reprogrammed During Egg and Sperm Development
Scientists at the Babraham Institute have gained a new understanding of when and how the DNA in developing egg and sperm cells is 'reset', in preparation for making a new embryo
It is well known that small molecular structures,
methyl groups, can be added to DNA that will alter
gene activity, these modifications to the DNA can
be acquired during development in the womb
and throughout adult life and can even
arise from changes in environment.
Most of these modifications are removed in immature egg and sperm cells in order to 'reset' the DNA to erase any 'environmental memory.' But some are not removed. Decoding this type of reprogramming has major implications in our understanding of development and how these methyl modifications can be inherited from one generation to another.
All the cells in the body of one individual have the same DNA sequence. How that DNA sequence is interpreted into the genes that form unique cell types, is determined by molecular switches that turn on and off various genes. One type of chemical modifier a methyl group when added at the beginning of a coding sequence, will turn that gene off, making it inactive.
The research, published in the journal Molecular Cell, is the first genome-wide study to look at what happens in these methyl groups during early egg and sperm cell (primordial germ cell) development. This field of research investigating molecular modifications to DNA, modifications which do not alter DNA's underlying sequence, is called epigenetics.
Dr Stefanie Seisenberger is lead author from the Babraham Institute, which receives strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC).
"In the process of producing a high resolution
map showing the location and timing of methyl
group removal from primordial germ cell DNA,
we discovered that the majority of demethylation
occurs much earlier than people previously thought
We can now shed light on the process of methyl
group removal in mammals, a mechanism
which has remained elusive for many years.
An even more exciting finding is that we have
identified regions of DNA that avoid demethylation
and are therefore candidates for how environmental
information can be transferred from parent to offspring.
Interestingly, one of these areas has a link
with type 2 diabetes."
Dr. Stefanie Seisenberger
According to Professor Wolf Reik, senior author of the paper, a Group Leader at the Babraham Institute and an associate faculty member at the Wellcome Trust Sanger Institute: "Several recent studies in other laboratories have confirmed that environmental information can be transferred from parent to offspring in mammals, for example mice fed a high-fat diet produce offspring with altered metabolic regulation, but it is not known how this occurs.
One interesting observation from our study,
which backs up work performed elsewhere,
is that incomplete removal of methyl groups
from DNA occurs more frequently in sperm
than egg forming cells, suggesting that fathers
have a bigger part to play in epigenetic
inheritance than previously thought.
This has implications not only for
understanding mechanisms of inheritance
and development but also our susceptibility
to obesity and diseases like diabetes."
Professor Wolf Reik
Part of the work performed in this study was carried out at the Wellcome Trust Sanger Institute under the new Associate Faculty scheme.
Professor Michael Wakelam, Director of the Babraham Institute, commented, "This is an excellent example of fruitful scientific collaboration between research institutes bringing about an improvement of our knowledge of how we develop, and thus paving the way for future epigenetics research into the inheritance of age-related diseases such as diabetes."
This research was supported by the BBSRC, Boehringer Ingelheim Fonds, MRC, Wellcome Trust and the EU.