Researchers at Fox Chase Cancer Center found that epigenetic changes, which are chemical modifications that affect gene activity without altering the DNA sequence, can reshape the way DNA is organized inside cells, a process increasingly linked to cancer and other diseases. The study showed that these changes can alter three-dimensional (3D) genome structure in ways that may influence cancer treatment. The findings were published in Nature Communications.
“Although every cell contains nearly 2 meters of DNA, it must be folded into a nucleus only a few micrometers wide,” said Rebecca G. Smith, a doctoral student at Fox Chase Cancer Center and Temple University, and first author of the study. “Our study helps explain how cells organize DNA in 3D space and how that structure changes in response to epigenetic signals.”
How Cells React to Epigenetic Signals
Working with collaborators at Fox Chase and UMass Chan Medical School, Smith used genomic and biochemical approaches to study how chromatin –the DNA-protein material that makes up chromosomes –affects the genome’s 3D organization.
“Our genome has to be both stable and flexible,” Smith said. “It needs to maintain its overall structure while remaining capable of responding to changes inside the cell. We found that not all cohesin molecules behave the same way. Some respond rapidly to epigenetic changes, while others remain remarkably stable, preserving key features of genome organization.”
Cohesin is a protein complex that helps fold DNA into loops and bring distant parts of the genome together. These loops influence which genes can interact with their regulatory elements and play a key role in controlling gene expression.
Some Parts of the Genome Change, While Others Stay Stable
The research team found that increasing histone acetylation – an epigenetic modification commonly altered in cancer –does not affect all cohesin-mediated structures the same way. Instead, it selectively weakens local DNA folding while leaving larger structural loops largely intact. That suggests cells may be able to remodel small parts of the genome without disrupting its overall architecture.
Senior author Yu (Sunny) Liu, PhD, Assistant Professor for the Nuclear Dynamics and Cancer Research Program and Cancer Epigenetics Institute at Fox Chase Cancer Center, said the work highlights both the scientific discovery and Smith’s contributions as an early-career researcher.
Potential Implications for Cancer Therapy
Histone acetylation is frequently disrupted in tumors, and drugs called histone deacetylase, or HDAC, inhibitors are already used to treat several cancers. By showing how these epigenetic changes reshape genome organization, the study may help researchers better understand how epigenetic therapies influence gene regulation and chromosome structure as well as help guide the development of more precise cancer treatments.
Read the full paper here: “Histone Acetylation Differentially Modulates CTCF-CTCF Loops and Intra-TAD Interactions”