Researchers have identified a DNA modification known as 5-formylcytosine (5fC), which acts as an activating epigenetic switch that initiates gene activity during early embryonic development. This discovery is groundbreaking as it reveals for the first time that vertebrates possess more than a singular type of epigenetic DNA marker, offering new insights into the regulation of genes in the initial phases of development.
Researchers have identified a DNA modification called 5-formylcytosine (5fC), which acts as an activating epigenetic switch that initiates gene activity during early embryonic development. This discovery is groundbreaking as it reveals for the first time that vertebrates possess more than a singular type of epigenetic DNA marker, offering new insights into the regulation of genes in the initial phases of development.
The findings were detailed in the journal Cell.
5fC is the second confirmed epigenetic DNA modification apart from methylcytosine
Our bodies consist of trillions of cells working in harmony to create a cohesive organism. All of us began as a single fertilized egg cell, which must replicate rapidly to develop into a complete human being, forming organs correctly and in their proper locations. This complex developmental process relies on thousands of genes being activated precisely at the right times and places. The mechanism of gene activation and deactivation is governed by what are known as epigenetic modifications—chemical groups added to DNA and its associated proteins that function like traffic signals, regulating whether genes are turned on or off.
For many years, scientists believed that vertebrates had only one type of epigenetic modification on DNA: cytosine methylation, which is linked to gene suppression. A decade ago, three additional chemical modifications were identified in vertebrate DNA, but due to their minimal presence, scientists were skeptical about their functional roles as epigenetic markers.
Recently, Professor Christof Niehrs and his research team demonstrated that one of these modifications, 5-formylcytosine, plays a crucial role in gene activation during early development. This finding is important because it confirms that vertebrates have multiple types of epigenetic DNA markers and reveals a new and previously unrecognized mechanism of gene regulation through epigenetics. “This research marks a significant advancement in epigenetics, as 5fC is only the second validated epigenetic DNA modification next to methylcytosine,” stated Niehrs, who is the Founding and Scientific Director of the IMB at Johannes Gutenberg University Mainz (JGU), established in 2011.
In their investigation, the researchers focused on 5fC within frog embryos. Through the utilization of microscopy and chromatography, they found that 5fC levels surged notably at the beginning of development during a critical phase known as zygotic activation when numerous genes are activated. Eleftheria Parasyraki, the lead author of the study, commented: “The sighting of 5fC in visible microscopic dots, or chromocenters, was fascinating. This led us to hypothesize that 5fC plays a vital role in early embryonic development.”
To confirm that 5fC functions as an activating epigenetic marker, the team modified enzymes in the embryos to enhance or reduce the levels of 5fC on the DNA. Elevating 5fC resulted in heightened gene expression, whereas diminishing it led to reduced gene expression, thus confirming that the presence of 5fC on the DNA is responsible for gene activation. Furthermore, the researchers also detected 5fC chromocenters in mouse embryos during zygotic gene activation, indicating that 5fC likely serves as an activating epigenetic marker in both mammals and frogs.
The discovery of 5fC’s role as an activating epigenetic regulator on DNA raises numerous questions regarding its specific functions and its implications beyond the early stages of zygotic genome activation. Notably, cancer cells often exhibit elevated levels of 5fC. Further research into 5fC is essential to address these inquiries, potentially enhancing our comprehension of developmental processes and the disruptions of gene regulation in diseases.
