Women are born with all of the eggs they will have, and maintaining those cells until it’s time to start releasing them is clearly a critical part of female fertility. New work has provided insight into how epigenetics, or chemical modifications to genes, helps keep those cells in stasis. Led by Dr. Gavin Kelsey of the Babraham Institute and colleagues in Dresden and Munich, a research team analyzed how a protein, MLL2, creates a unique pattern of epigenetic marks that keep cells in a suspended state. The work was reported in Nature Structural and Molecular Biology.
If the egg cells carried by a girl at the start of life are not put into stasis throughout childhood, they will never get the chance to become mature eggs, and will not be able to create a pregnancy. The researchers wanted to see how epigenetics played a role in this process, but these tags are very challenging to study in egg cells because there aren’t many of these cells. As such, the team had to create new ways to find epigenetic marks that were incredibly sensitive and would be able to identify such tags in only a handful of cells. These marks can act to control whether genes are turned on or not.
With their new approach, the investigators saw that as egg cells develop, an epigenetic mark referred to as H3K4me3 spreads through the genome of those cells. While that marker has already been identified and influences gene activation in many kinds of cells in the body, this role in egg cells is a novel finding. The researchers also found that the MLL2 protein acts to place these H3K4me3 marks in egg cell genomes. When MLL2 is absent, the majority of H3K4me3 tags are lost from egg cells, and the cells die before they can be used at a time of sexual maturity; the chance for offspring is lost.
"Our findings show that H3K4me3 is created in two ways. MLL2 can add the H3K4me3 mark without any nearby gene activity while another process, that doesn't use MLL2, places the same mark around active genes. By studying this new mechanism we hope to expand our knowledge of epigenetics in general as well as adding to our understanding of fertility,” said the first author of the report, Dr. Courtney Hanna.
"We are only beginning to unravel the details of the connection between epigenetics and egg development, a fundamental aspect of biology that may play a part in transmitting information from mother to fetus. Discoveries like this highlight some of the unusual biological processes that take place in these highly important cells,” noted lead scientist Dr. Kelsey.
For more information on epigenetic tags and how they influence gene expression, check out the video below from the Garvan Institute of Medical Research.