Caenorhabditis elegans at different developmental stages (eggs, larvae, adults).
Image Credit: © F.X Stubbe, UNIGE
Scientific Frontline: Extended "At a Glance" Summary: Transgenerational Epigenetic Inheritance
The Core Concept: Transgenerational epigenetic inheritance refers to the process by which biological traits are passed down to offspring without altering the underlying DNA sequence.
Key Distinction/Mechanism: Unlike traditional genetic inheritance, which relies on changes to the DNA itself, epigenetic inheritance involves reversible modifications to gene regulation, such as altering the histones that package DNA, which dictates how accessible genes are to cellular proteins.
Major Frameworks/Components:
- Epigenetics: The modulation of gene activity without altering DNA.
- Histone Modification: Specifically, the H3K27me3 mark, which represses certain genes.
- Caenorhabditis elegans: A nematode worm commonly used as a model organism in biological research due to its rapid reproduction cycle.
- Sustained Impact: The study revealed that disrupted gene regulation (resulting in reduced fertility) persisted in genetically normal descendants for at least fifteen generations after the initial epigenetic trigger was removed.
- Dual-Mechanism Maintenance: Researchers identified two successive mechanisms required to establish and then maintain this new epigenetic state across generations.
Branch of Science: Molecular Biology, Cellular Biology, Genetics, and Epigenetics.
Future Application: Understanding these mechanisms could provide a framework for how organisms adapt to environmental changes independent of slow genetic evolution, potentially impacting agricultural resilience, disease etiology, and evolutionary biology.
Why It Matters: This study demonstrates that heredity is more complex than DNA alone, proving that a temporary environmental or regulatory disruption can leave a lasting biological imprint across dozens of generations.
A UNIGE study shows that a temporary change in gene regulation can be inherited for at least fifteen generations in the worm C. elegans, without any change to the DNA sequence.
The transmission of biological traits from one generation to the next is generally attributed to DNA. But could some changes be passed on without altering the DNA sequence? Scientists at the University of Geneva (UNIGE) have shown that, in nematodes—roundworms with long, thin bodies—a temporary change in gene regulation can persist for many generations, even though the descendants no longer carry the genetic element that initially triggered the change. These findings, published in the EMBO Journal, provide new insights into the mechanisms underlying epigenetic inheritance.
Every cell in an organism contains the same DNA, which carries all the instructions needed for it to function. Yet cells do not all use the same genes: a nerve cell, for example, does not activate the same genes as a muscle cell. Epigenetics refers to the mechanisms that allow gene activity to be modulated without changing the DNA sequence.
These mechanisms involve, among other things, subtle and reversible modifications to the proteins that package and organize DNA. They can alter how DNA is organized—but not its content—and affect the accessibility of genes to cellular proteins. Some of these modifications can persist when cells divide and, in some cases, can be passed onto the next generation.
This type of inheritance could represent an additional mechanism allowing organisms to respond and potentially adapt to changing environmental conditions.
A Temporary Change with Lasting Effects
To determine how long an epigenetic change can persist across generations, the team led by Florian Steiner, a professor in the Department of Molecular and Cellular Biology at UNIGE’s Faculty of Science, studied Caenorhabditis elegans. This tiny worm has become a major model organism in biology, thanks to the many discoveries of fundamental biological mechanisms it has enabled. Its rapid reproduction also makes it possible to easily follow several generations in the laboratory.
The scientists focused on a modification of histones—the proteins around which DNA is wrapped—known as H3K27me3. This epigenetic mark is associated with the repression of certain genes, meaning that it helps prevent them from being expressed. The researchers temporarily disrupted the distribution of H3K27me3 by causing the worms to express a mutated form of the H3.3 histone. This initial disruption led, among other effects, to reduced fertility, from around three hundred offspring per parent to one hundred or even fifty. However, it was not genetically inherited: the descendants were genetically normal. The scientists then followed gene regulation and fertility from one generation to the next.
“Surprisingly, we found that the effects did not disappear when the initial trigger was gone. In the descendants, which were genetically normal, the changes in gene regulation and the fertility defects persisted for at least fifteen generations!” explain Isa Özdemir and François-Xavier Stubbe, a PhD student and a postdoctoral researcher in Professor Steiner’s group, respectively, and co-first authors of the study.
The scientists then sought to understand how this information could be maintained for so long. The team identified two mechanisms that act successively. The first is required to establish the new epigenetic state following the initial disruption. The second then allows this state to be maintained across generations. “Our results show that maintaining an epigenetic state relies on a succession of specialized mechanisms, rather than on a single process,” explain Isa Özdemir and François-Xavier Stubbe.
A Form of Heredity Independent of DNA
“A temporary disruption of gene regulation can leave a lasting and transmissible imprint, even though the genetic change that initially caused the disruption has disappeared in the descendants. This type of inheritance could represent an additional mechanism allowing organisms to respond and potentially adapt to changing environmental conditions,” concludes Florian Steiner.
Published in journal: EMBO Journal
Title: Transgenerational inheritance of altered H3K27me3 in wild-type Caenorhabditis elegans
Authors: Isa Özdemir, François-Xavier Stubbe, Kamila Delaney, Joanna M Wenda, and Florian A Steiner
Source/Credit: Université de Genève
Edited by: Scientific Frontline
Reference Number: mbio092826_01