Epigenetics refer to DNA modifications that may affect phenotype but don’t alter the nucleotide sequence itself. Epigenetic changes can often be passed down generations, hence the Greek prefix “epi”, to indicate heritable mechanisms “in addition to” genetics. Various factors, from time to a person’s habits, can leave epigenetic marks, and these, in turn, can influence phenotypes that scientists can observe and measure—they can even cause diseases. Catch up on the some of the latest breakthroughs in epigenetics research in this article.
The Effects of Epigenetic Modifications Are Far-Reaching and Heritable
Epigenetic modifications include a wide range of chemical and structural changes to DNA. The epigenome, which encompasses all of a cell’s, or an organism’s, epigenetic modifications, plays an important role in regulating gene expression. Enzymes such as histone acetyltransferase or DNA methyltransferase could deposit chemical marks on histones, which are proteins that package DNA, or directly on nucleotides, respectively. Scientists have also found evidence that both epigenetic marks that accumulate throughout a parent’s life and in the womb can be passed down to future generations. Considering the epigenome’s far-reaching effects, its dysregulation could result in diseases, including cancer and cardiovascular disorders. Today, researchers can investigate the epigenome using various next-generation sequencing methods. Many are also working to develop CRISPR-based technologies to edit the epigenome.
Epigenetic differences in identical twins result in distinct gene expression profiles.
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Epigenetic Differences in Identical Twins
Scientists have long observed that even identical twins can have distinct behavioral tendencies and susceptibilities to diseases. Since the 1990s, researchers had suspected that epigenetics likely underlie differences between monozygotic twins, who share identical DNA sequences. In the early 2000s, geneticist Tim Spector at King’s College London sequenced the epigenomes of twins and found differences in the content and distribution of epigenetic modifications, even between identical twins. Decades later, epigenomics researcher Jordana Bell, also of King’s College London, and her team wanted to know if epigenetics could explain why one sibling in a twin pair developed a disease while the other did not. By analyzing twins’ epigenomes, Bell’s team discovered epigenetic differences that are associated with breast cancer, obesity, and type 2 diabetes.
An Epigenetic DNA Marker’s Derivative Is More than Just an Intermediate
Most epigenetic marks are on histones rather than on DNA itself. Until recently, scientists had only observed one epigenetic DNA marker: 5-methylcytosine (5mC). But molecular biologist Christof Niehrs at the Institute of Molecular Biology in Mainz recently found that 5-formylcytosine (5fC), a derivative of 5mC, could also act as a DNA epigenetic marker. Before this, scientists thought that 5mC derivatives were mere pathway intermediates. However, in their 2024 Cell study, Niehr’s team found that in frog embryos, 5fC, but not other 5mC derivatives, promoted protein synthesis by associating with RNA polymerase III. Their finding demonstrated that 5fC is not just 5mC’s intermediate—it could also act as an epigenetic DNA marker.
A new tool, called epigenomic tomography, offers a more accessible way to detect spatial patterns of epigenetic marks and brain function.
©iStock, nopparit
Epigenetic Brain Scan Offers a More Accessible Way to Identify Spatial Patterns
Cutting-edge tools in epigenomic sequencing can be expensive and difficult to use. So Chang Lu, a chemical engineer at Virginia Tech, and his team sought to develop a more accessible method to investigate the cells’ epigenome. Lu’s alternative approach, called epigenomic tomography, scans spatial patterns of the epigenome by cutting thin slices of tissue and running bulk epigenomic sequencing on these slices. As a proof of concept, Lu’s team compared the epigenome in brains of mice with and without induced seizures. They found distinct spatial patterns of epigenetic marks between the two groups, as expected, since seizures often disrupt brain function spatially. This indicates that although epigenomic tomography sacrifices the near-single-cell resolution offered by other approaches, the tool can still detect spatial patterns across larger areas in the brain.
Epigenetic Editing Could Silence Bad Cholesterol Receptors in Mice Long-Term
Epigenetic regulation can influence a lot of functions in the body, including how it metabolizes cholesterol. Recently, Angelo Lombardo, a geneticist at the San Raffaele Telethon Institute for Gene Therapy, and his team developed an epigenetic editing strategy that targeted Pcsk9. The gene encodes for a protein that regulates the amount of cholesterol receptors in the body—researchers have previously found that silencing this gene could reduce the level of low-density (“bad”) cholesterol in the blood. In their study, Lombardo’s team silenced Pcsk9 in mouse livers by delivering gene transcription repressors via nanoparticles. They found that this reduced the level of bad cholesterol in the blood of mice that received the treatment by about 35 percent. The researchers also discovered that nearly a year after the experiment, Pcsk9 expression was still about 40 percent less than their untreated counterparts, indicating that the effects of this treatment could last for a while.
Fyodor Urnov studies genome and epigenome editing at the University of California, Berkeley. He is also the Scientific Director at the Innovative Genomics Institute, and a Co-Founder of Tune Therapeutics.
D.L. Anderson
Epigenetic Editors Are Revolutionizing Medicine
Recent technological breakthroughs in epigenomic editing have enabled scientists to bring discovery-based ideas from past decades to live. Researchers in academia and industry are now exploring possibilities to use epigenetic editing to alleviate various conditions, including chronic pain, inflammation, viral infections, and cardiovascular disorders. For example, an ongoing clinical trial investigates the use of lipid nanoparticle-delivered epigenome editors to silence hepatitis B virus activity in the liver. This effort, led by the biotech company Tune Therapeutics, was the first infectious disease epigenetic therapy to enter clinical trials.
