For the first time, researchers have been able to map the spatial organization of DNA in the human cell. The inner surface of the cell nucleus plays a crucial role in this organization. Large blocks of DNA containing inactive genes are attached to this inner surface. This is reported by Dr. Bas van Steensel and co-workers at the Netherlands Cancer Institute in Amsterdam in the scientific journal Nature (Advanced Online publication, 7 May 2008).
The spatial organization of DNA is an intriguing problem. For decades, scientists have tried to elucidate how the genetic material of a human cell, consisting of a few dozen strands of DNA with a combined length of two meters, is stored inside a cell nucleus of only one-hundredth of a millimeter. This is similar to fitting a wire of four kilometers long into a sphere the size of a marble.
Now, Dr. Bas van Steensel and colleagues of the Netherlands Cancer Institute have succeeded in constructing a highly detailed, genome-wide view of the spatial organization of DNA in a human cell. To do so, they used a clever molecular tagging technique and specially designed DNA chips. Previously, Van Steensel and co-workers already managed to map the organization of the genetic material of the fruit fly (Nature Genetics, 30 July 2006).
Van Steensel and colleagues now demonstrate that the DNA strands in the human cell nucleus are structured into segments that attach to the nuclear lamina. This is a protein network that coats the inner surface of the nuclear membrane. The genome researchers discovered that the lamina does not bind random pieces of DNA, but rather very large, clearly demarcated blocks that contain inactivated genes. These blocks are up to 50 times larger than the DNA segments that bind to the nuclear lamina in fruit fly cells.
Dr. Bas van Steensel: “We discovered special molecular signatures at the edges of these DNA blocks, suggesting that the spatial organization of the DNA is in fact encoded in the DNA itself. Furthermore, we observed that these blocks contain genes that are inactive. We think that the binding to the lamina may play a role in keeping these genes inactive. It’s fascinating to think that the positioning of genes in the genome is non-random. Apparently, genes that have no function in a given cell type are stowed at the rim of the nucleus and kept inactive, while active genes are located in the center of the nucleus.”
This study was supported by the Netherlands Organization for Scientific Research, the Dutch Cancer Society, and a European Young Investigator Award.