Egg cells, or oocytes, are made inside a female’s body before she is even born and they must be kept in a state of equilibrium or stasis during her childhood. Eventually, they can transition to mature eggs when needed as an adult. If the eggs do not go into stasis, however, they will never be able to eventually form into a baby. New research in Nature Structural and Molecular Biology explores the influence of epigenetics on egg cell stasis and the importance of histone modifications.
Getting the egg into stasis entails adding on numerous epigenetic marks along its DNA. These chemical tags control which genes are turned “on” or “off.” A team of researchers led by Gavin Kelsey, PhD, at the Babraham Institute in Cambridge, UK, and a group of colleagues from the Technische Universität Dresden and the Institute of Computational Biology in Munich investigated how a protein known as MLL2 creates a distinct pattern of epigenetic tags that are necessary to place egg cells into stasis.
“By studying this new mechanism we hope to expand our knowledge of epigenetics in general as well as adding to our understanding of fertility,” commented first author Courtney Hanna, PhD.
Histone acetylation of H3 and H4 is involved in the regulation of chromatin structure and the recruitment of transcription factors to gene promoters, among many other processes. MLL2, or Lysine Methyltransferase 2D in humans, is a histone methyltransferase that methylates the Lys-4 position of histone H3. MLL2 is implicated in the proper development of muscle tissue, the heart, and B-cells.
In this study, they assessed a few histone modifications, including histone H3K4 trimethylation, histone H3K27 acetylation, and histone H3K27 trimethylation. Since it’s very difficult to study oocytes because there are very few of them, the group developed a low-input chromatin immunoprecipitation (ChIP) assay to interrogate H3K4me3, H3K27ac and H3K27me3 marks throughout oogenesis.
As the eggs grew, they discovered that a popular histone modification mark known as H3K4me3 spread throughout the genome. The same mark has previously been shown to exist near the beginning of active genes in numerous cells. However, its role in egg cells was found to be different. Without this protein, a majority of H3K4me3 marks were lost and the egg cells could no longer survive.
There are two ways in which H3K4me3 can be formed, according to the results. First, the epigenetic mark can be added by MLL2 without gene activity nearby. Second, H3K4me3 can be added around active genes via another process without the use of MLL2.
“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,” Kelsey said. “Discoveries like this highlight some of the unusual biological processes that take place in these highly important cells.”
Source: Hanna, C.W. et al. (2018). MLL2 conveys transcription-independent H3K4 trimethylation in oocytes. Nature Structural & Molecular Biology, 25:73-82.
Reference: Babraham Institute. Keeping egg cells fresh with epigenetics. 9 Jan 2018. Web.
