The nucleus is the control center of the cell, packed with 6 linear feet of DNA in a space narrower than the width of a human hair. Since it began, research supported by the 4D Nucleome (4DN) program has improved our understanding of how DNA is packaged and organized in the crowded space of the nucleus. Advancements by the program have prompted scientists to develop new methods to get an even clearer picture of how the DNA is organized. These methods are beginning to give us a good grasp on how large areas of DNA are packaged into different compartments, where portions of DNA that would be far apart in a piece of DNA stretched out long, are actually located close to each other in the nucleus, similar to if you scrunched up a long piece of string and placed it in a ball. Understanding how DNA is organized in three dimensions has informed scientists how that organization can alter which genes are turned on or off, an important factor in many diseases such as cancer. We can now see how large portions of DNA are situated, but can more information be gathered by looking at how smaller regions of DNA in the nucleus are organized?
A team of researchers led by Drs. Xavier Darzacq and Job Dekker, whose research is supported by the 4DN program, developed a new method, called Micro-C, to provide a better image of how smaller regions of DNA are organized in three dimensional space. Looking at the DNA in a mouse model system, the team demonstrated that smaller-than-previously-thought regions of DNA can control gene activity and that the closeness of these small regions is important in recruiting proteins to control how genes are turned on or off. A companion study mirrored these studies demonstrating that Micro-C is suitable for human cells as well. The development of this new method will help strengthen our understanding of how genes are spatially controlled in the crowded nucleus and may provide opportunities for developing future treatments as we learn more about gene activity regulation in healthy and diseased cells.
References
- Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding. Tsung-Han S Hsieh, Claudia Cattoglio, Elena Slobodyanyuk, Anders S Hansen, Oliver J Rando, Robert Tjian, Xavier Darzacq. Molecular Cell, 2020 May 7. 78, 539-553
- Ultrastructural Details of Mammalian Chromosome Architecture. Nils Krietenstein, Sameer Abraham, Sergey V Venev, Nezar Abdennur, Johan Gibcus, Tsung-Han S Hsieh, Krishna Mohan Parsi, Liyan Yang, René Maehr, Leonid A Mirny, Job Dekker, Oliver J Rando. Molecular Cell, 2020 May 7. 78, 554-565
