The study, published in the journal Nature Genetics, found that genes that are replicated early in the cell cycle are more likely to form compact, folded structures, while genes that are replicated late are more likely to form open, extended structures. This difference in folding appears to be related to the activity of a protein called CTCF, which is known to play a role in organizing the genome into loops.
"Our findings suggest that the timing of DNA replication may be an important factor in determining how genes are folded and regulated within the nucleus," said study leader Davide Levens, PhD, professor of biochemistry and biophysics at UCSF. "This could have important implications for understanding how the genome is organized and regulated, and for developing new treatments for diseases caused by DNA damage."
The researchers made their discovery using a new technique called Hi-C, which allows scientists to measure the physical interactions between different regions of the genome. Using Hi-C, they were able to show that genes that are replicated early in the cell cycle are more likely to interact with each other and form compact, folded structures, while genes that are replicated late are more likely to interact with other genes that are located further away and form open, extended structures.
This difference in folding appears to be related to the activity of CTCF, which is a protein that helps to organize the genome into loops. CTCF binding sites are more common in genes that are replicated early in the cell cycle, and CTCF binding appears to be required for the formation of compact, folded gene structures.
"Our findings suggest that CTCF may play an important role in organizing the genome into loops and regulating gene expression," said Levens. "This could have important implications for understanding how the genome is regulated, and for developing new treatments for diseases caused by DNA damage."
The researchers believe that their findings could have important implications for understanding a variety of diseases, including cancer and neurodegenerative disorders. In cancer, for example, DNA replication is often disrupted, which could lead to changes in gene folding and gene expression that contribute to the development of cancer.
"Our findings suggest that the timing of DNA replication may be an important factor in the development of cancer and other diseases," said Levens. "We hope that our research will lead to new insights into the causes of these diseases and the development of new treatments."
