Shaping the stem cell genome

25 July 2013

Stem cell genes seek each other in the cell nucleus. So a study by the Hubrecht Institute in Utrecht, the Netherlands, has found, published this week in Nature. 'It’s a new way of looking at DNA.'

Prof. Dr. Wouter de Laat of the Hubrecht Institute and his colleagues have shown that DNA strings in embryonic stem cells are folded in a unique manner. The DNA appears to be folded in such a way that all ‘stem cell genes’ are located close to each other. The activity of these genes ensures that stem cells remain stem cells and they do not change into other types of cells.

The so-called stem cell factors are responsible for the special DNA folding in embryonic stem cells. These are proteins that can only be found in stem cells and with which normal cells can be reprogrammed into stem cells. Without these proteins, stem cells lose their unique DNA folding. The proteins attach to DNA strings in various places and ‘pull’ the strings together.

'We don’t know exactly why these genes have to be so close to each other”, says de Laat. “But of course it’s entirely possible that this will allow the stem cell genes to be sequenced in an improved and more stable manner. It makes stem cells more robust.'

The findings by de Laat and his colleagues underline the importance of the three-dimensional organization of DNA strings. It was previously thought that only the sequence of the genetic letters in the DNA was important. But it seems that it is important for genes with a comparable role to literally be close to each other. 'This is a new way of looking at DNA. The spatial organization of the DNA actually forms an additional control layer.'

De Laat and his colleagues outline their findings on July 24, 2013 in Nature. Biologist Prof. Dr. Wouter de Laat is group leader at the Hubrecht Institute. He specializes in making DNA folding in the cell nucleus visible. In the long run, the findings from the study will contribute to ‘regenerative medicine’ and could lead to new insights into the origins of diseases. The Hubrecht Institute is a research institute of the Royal Netherlands Academy of Arts and Sciences and collaborates closely with University Medical Center Utrecht.
Wit E de, Bouwman BAM, Zhu Y, Klous P, Splinter E, Verstegen MJAM, et al. The pluripotent genome in three dimensions is shaped around pluripotency factors. Nature 2013 doi:10.1038/nature12420