How maternal and paternal chromosomes get along after fertilization?

How maternal and paternal chromosomes get along after fertilization?

A research team has identified a mechanism by which the fertilized egg balances out the differences between chromosomes inherited from the mother and the father. The study, now published in the scientific journal EMBO reports, may pave the way for future developments in the clinical management of infertile couples.

The fertilization of an egg by a sperm cell marks the beginning of a new life. However, many of the molecular mechanisms behind this extraordinary process remain a mystery.

It is well known that mother and father pass on their genetic information in a different manner. While the maternal chromosomes in the egg are still undergoing division, the paternal chromosomes carried by the sperm have both completed their division and been substantially compacted to fit into the small volume of the sperm cell. The mechanisms through which the fertilized egg levels these differences between parental chromosomes - an essential aspect for the correct initiation of embryo development - are largely unknown.

The team uncovered a protein called dMLL3/4 that allows the fertilized egg to ensure both the correct division of the maternal chromosomes and the unpacking of the paternal genetic information. In the absence of dMLL3/4, oocytes develop normally but fail to initiate the embryo mitotic divisions after fertilization. This incapability results from defects in paternal genome reprogramming and maternal meiotic completion. The methyltransferase activity of dMLL3/4 is dispensable for both these processes.

Authors further show that dMLL3/4 promotes the expression of a functionally coherent gene subset that is required for the initiation of post‐fertilization development. They identify the evolutionarily conserved IDGF4 glycoprotein (known as oviductin in mammals) as a new oocyte‐to‐embryo transition gene under direct dMLL3/4 transcriptional control. 

" dMLL3/4 is a gene expression regulator, therefore, it has the ability to instruct cells to perform different functions. We observed that dMLL3/4 promotes, still during egg development, the expression of a set of genes that will later be essential for balancing out differences between the chromosomes inherited from the mother and from the father," explains the author.

"These results open the door to new diagnostic approaches to female infertility, and to possible improvements in embryo culture media formulations for assisted reproduction techniques," adds the author.

"The dMLL3/4 protein was identified using fruit flies (Drosophila melanogaster) as a model organism, which again reinforces the importance of basic research and the use of model organisms as critical stepping-stones for translational research and the improvement of human health", concludes the author.