Epigenetics

Epigenetics

Each cell in our body contains the same genetic information—that is, all the genes, even those it doesn’t need. For example, skin cells carry the genes needed to produce digestive enzymes. And yet, we don’t digest with our skin! So, how do cells know which genes to use and which ones to keep "switched off"?

Epigenetics is the science that studies changes in gene activity without altering the DNA sequence itself. These changes can influence how the DNA is read. There are three main ways to turn a gene on or off: by adding small chemical groups (epigenetic marks) directly onto the DNA, by modifying the proteins around which DNA is wrapped (called histones), or by using small non-coding RNAs—molecules that can bind to the DNA to regulate its activity.

Epigenetics plays a major role in reproductive biology because it is involved in fertility, reproductive health, and the development of future generations. Many studies conducted by members of the RQR aim to understand epigenetic regulation.

At the beginning of human development, the DNA undergoes major epigenetic changes. One of the most significant is the widespread addition of chemical markers called methyl groups, which act to "silence" certain genes or undesirable DNA elements. These marks, established very early, remain largely stable throughout life. To better understand this process, William Pastor and his team use stem cell–based models to study how these marks are added and organized in the genome. Werner Giehl Glanzner investigates the epigenetic regulators involved in the earliest stages of embryonic development, including the role of microRNAs and DNA methylation in embryonic genome activation. Julie Brind’Amour studies the mechanisms of epigenetic reprogramming that erase and re-establish the mother’s epigenetic marks during the early stages of embryonic development.

Environmental exposures

Epigenetic marks can accumulate over the course of life and may even be passed on to the next generation. Sarah Kimmins explores how the environment—especially diet and toxins—affects gene expression in parents and can be transmitted to their children, highlighting the importance of paternal health before conception.

Géraldine Delbès studies how exposure to medical or environmental substances during sensitive periods of life can impair male fertility by disrupting the epigenetic inheritance passed on to future generations.

Serge McGraw’s team investigates the role of epigenetic dysregulation in developmental and neurodevelopmental disorders, particularly when the fetus is exposed to alcohol during prenatal life.

The use of assisted reproductive technologies raises questions about the environment to which embryos are exposed during the first days of life in a lab dish, and how this might influence long-term health. Sophie Petropoulos investigates how the culture conditions of embryos in in vitro fertilization (IVF) can alter their development through epigenetic mechanisms, with lasting effects on the child’s health. Lawrence C. Smith studies how cellular manipulations, such as cloning or the use of stem cells, affect the epigenetic marks transmitted to the embryo. Jacquetta Trasler studies how the environment can cause congenital malformations through epigenetic regulation, particularly in children conceived through assisted reproduction or when the father is exposed to medications or chemical substances.

Regulation of gene expression

Jacques Drouin seeks to understand how certain genes are regulated in the pituitary gland, an endocrine gland located at the base of the brain, through epigenetic mechanisms. More recently, he has also begun to explore the potential role of these mechanisms in oocyte maturation.

Raj Duggavathi’s team studies the role of histone modifications in gene expression in granulosa cells of the ovaries.

X chromosome inactivation

Unlike males, who have XY sex chromosomes, females have two X chromosomes (XX). To prevent female cells from expressing twice as many X-linked genes as male cells, one of the two X chromosomes is "shut down" very early in embryonic development. Bernhard Payer focuses on the phenomenon of X chromosome inactivation—an epigenetic mechanism that balances gene expression between males and females. He also studies how the X chromosome can be reactivated during egg cell formation.

Animal production

Epigenetics is important not only for human health but also in the field of animal production. Isabelle Gilbert studies epigenetics in the sperm of livestock animals to better understand what affects fertility and to improve semen preservation methods. Marc-André Sirard examines how the mother’s metabolic status influences the epigenome of the egg and the embryo, which could help explain certain fertility or dairy production issues in cattle.

To study how cells are reprogrammed, particularly in pigs and cows, Vilceu Bordignon observes the early stages of embryonic development. He uses a technique called nuclear transfer, which involves inserting the nucleus of an adult cell into an egg cell whose own nucleus has been removed. This method has shown that a specialized cell can return to a “young” state, capable of becoming any type of cell.