Breakthrough Discovery of DNA “Range Extenders” Sheds Light on Gene Activation

Irvine, Calif., July 2, 2025 — In a significant breakthrough, researchers from the University of California, Irvine, have uncovered a previously unknown DNA element that plays a crucial role in gene activation across vast genomic distances. This discovery, detailed in a study published in Nature, could reshape our understanding of genetic regulation and its implications for human health.

Led by Assistant Professor Evgeny Kvon and graduate student Grace Bower, the research team identified what they have termed “Range Extenders” — DNA elements that facilitate communication between distant enhancers and their target genes. This finding marks a pivotal advancement in the field of genetics, addressing a question that has puzzled scientists for decades: how do cells know which genes to activate, and when?

The Role of Enhancers and Range Extenders

Enhancers are stretches of DNA that act as switches to turn genes on, but their ability to function over long distances has remained a mystery. While it is known that DNA folding by structural nuclear proteins can bring enhancers and genes closer together, this alone does not fully explain long-range gene activation. The discovery of Range Extenders offers a new perspective.

“Our work tackles the longstanding question in gene regulation: how do enhancers activate genes over distances that can sometimes exceed millions of base pairs?” said Assistant Professor Evgeny Kvon, the study’s senior and corresponding author. “In this study, we identified one of the missing factors: a previously uncharacterized class of regulatory DNA elements called Range Extenders.”

Experimental Evidence and Implications

To validate their hypothesis, the Kvon lab used precision genetic tools to engineer mouse models with enhancers relocated far from their target genes. The results were striking. Normally inactive enhancers became effective when paired with a Range Extender, successfully activating genes over distances exceeding 840,000 base pairs.

“The biggest challenge was ensuring that our discovery was not an artifact,” Kvon explained. “With any unexpected finding, the first question is always whether the observed phenomenon is due to alternative explanations.”

At the molecular level, Range Extenders contain short, repeating DNA sequences that appear to serve as docking sites for proteins that help form DNA loops, bringing faraway regions of the genome into close contact. This suggests that Range Extenders could be a widespread and fundamental part of gene regulation.

Potential Impact on Human Health

The implications of this discovery are profound. Disruptions in long-range enhancer activity are linked to various human diseases, including birth defects and cancer. By identifying Range Extenders, researchers now have a new class of genomic elements to explore as potential contributors to these conditions.

The findings also hold promise for enhancing the design of gene therapies and synthetic biology applications, where precise control over gene activation is crucial. This could lead to more effective treatments for genetic disorders.

Future Research and Broader Implications

“Our study raises several questions for future research,” Kvon added. “One is whether similar Range Extender elements operate in other cell types of the organism. The other concerns the nature of the molecular mechanism that enables the Range Extender to facilitate remote enhancer-promoter communication.”

This discovery underscores the importance of basic research and the federal NIH funding that supported it. Advancements like this, which lay the groundwork for future medical breakthroughs, are only possible through sustained investment in science that seeks to understand life at its most fundamental level.

The Kvon lab’s work not only solves a decades-old mystery but also opens the door to entirely new ways of thinking about how the genome is wired, and how we might one day rewire it to improve human health.

About the University of California, Irvine Charlie Dunlop School of Biological Sciences

Recognized for its pioneering research and academic excellence, the Charlie Dunlop School of Biological Sciences plays a crucial role in the university’s status among the nation’s top 10 public universities, as ranked by U.S. News & World Report. It offers a broad spectrum of degree programs in the biological sciences, fostering innovation and preparing students for leadership in research, education, medicine, and industry. Nestled in a globally acclaimed and economically vibrant community, the school contributes to the university’s impact as Orange County’s largest employer and a significant economic contributor. Through its commitment to exploring life’s complexities, the Dunlop School embodies the UC Irvine legacy of innovation and societal impact.

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