Scientists at the Salk Institute have identified that DNA structure constantly shifts within human cells. This dynamic folding process directly influences gene expression and may drive cancer progression. The findings appear in Nature Genetics and suggest new targets for treating genetic diseases.
Study Overview
Jesse Dixon, MD, PhD, led the research team examining the three-dimensional organization of the genome. The study reveals that loops in DNA form and break apart continuously rather than remaining static. This movement dictates whether specific genes activate or remain silent during cellular processes.
Researchers reduced levels of the protein NIPBL to test how folding dynamics affect cell function. Without this protein, cohesin could not move effectively along the DNA strand. The genome began to unfold unevenly, with some regions changing within minutes while others took hours.
"There are six billion base pairs in your genome," Dixon said. "What is interesting is that this folding does not just happen once and then the genome stays put." His team observed that rapidly changing regions correlated with active genes used by the cell.
Cell Identity
The investigation included heart cells and neurons created from human induced pluripotent stem cells. Dynamic DNA folding proved essential for regions tied to each cell type specific role. Genes critical for heart function behaved this way in heart cells while neuron-related genes did the same in brain cells.
"One thing this appears to suggest is that the continuous folding and unfolding of our genome may be particularly important for helping a cell remember who it is supposed to be," said first author Tessa Popay, PhD. This mechanism helps cells maintain their identity over time. Repeated formation of DNA loops reinforces these identity-defining gene patterns.
Disease Implications
Scientists believe errors in this machinery lead to syndromic conditions like Cornelia de Lange syndrome. Cancer potentially exploits this principle to manipulate cell identity and encourage uncontrolled growth. Correcting harmful folding patterns opens the door to future treatments for these conditions.
Funding for the project came from the National Institutes of Health and several private foundations. The study included researchers from UC San Diego alongside Salk Institute staff. These resources supported the extensive data collection required to map genome dynamics. Global healthcare systems face significant costs managing these conditions.
