MRC Human Genetics Unit scientists have discovered what it takes to change the location of a gene inside of the cell nucleus: December 2014
Scientists from the MRC Human Genetics Unit have discovered what it takes to change the location of a gene inside of the cell nucleus.
It has been know for more than a decade that the human genome is not randomly organized inside of the cell nucleus and that the three-dimensional organization of genes and chromosomes is linked to their function. In particular, the most inactive chromosomes and gene regions are preferentially found at the outer edge of the nucleus where they are packaged into very tight structures. When these genes become active during development they relocate from the periphery to the centre of the nucleus. But it was not clear whether these gene regions change address in order to be activated, or just because they are activated.
Using tools of synthetic biology, the researchers designed proteins to artificially switch on genes located at the edge of the nucleus, in stem cells where these genes would normally be silent. The act of switching the genes on, or even just unpacking their tight structure, was sufficient to cause the genes to change their position in the nucleus. Moreover, when the original trigger for this event was taken away, the gene regions continued to remember their new address.
Our findings provide clear evidence to link the three-dimensional organization of the mammalian genome with gene function and may be particularly relevant for understanding how this is changed as stem cells differentiate into different cell types in the body.
Chromatin decondensation is sufficient to alter nuclear organization in embryonic stem cells. Therizols P, Illingworth RS, Courilleau C, Boyle S, Wood AJ, Bickmore WA. Science. 2014 Dec 5;346(6214):1238-42. doi: 10.1126/science.1259587. PMID: 25477464