An Entire Galaxy to be Explored
(January 18th, 2016) Who would have thought there’s a beautiful galaxy inside our cells – you only have to make it visible. A new method for unveiling thousands of contact points between genes in 3D takes you on a journey into space, revealing new insights into mouse development along the way.
Within the genome, there are short- and long-range interactions, forming 3D configurations, whereby different parts of the genome come into contact with each other. Sarah Elderkin at the Babraham Institute in Cambridge, UK, and colleagues took a close look at more than 22,000 genes and showed how some key-decision genes, which specify the embryo’s development, are physically clustered and silenced in the nucleus of embryonic stem cells (ESCs).
All cells forming an embryo are derived from ESCs. These cells are able to replicate indefinitely and are maintained in an ‘undifferentiated state’, i.e., they have the potential to develop into any cell type in the body. To differentiate into a particular cell type, ESCs lose the stem cell state and progress along the developmental pathway into a specialised cellular identity. On the genomic level this means that specific developmental genes must be switched on. Conversely, remaining in the stem cell state requires the repression of such developmental genes.
Using a novel technique developed at the Babraham Institute (Promoter Capture Hi-C), the researchers identified a strong 3D network of developmental genes in ESCs, which are clustered together and thereby kept silenced. Holding the developmental genes together is a protein complex called Polycomb repressive complex 1 (PRC1), acting thus as a master regulator of ESC genome architecture by organising genes in three-dimensional interaction networks. It is this organisation that keeps specific ESC genes silenced, ensuring the maintenance of the stem cell state. Consequently, the researchers propose that a selective release of genes from this spatial network leads to their expression, controlling the specification of cell fate during early embryonic development.
This research uncovers a mechanism for how inappropriate expression of developmental genes is prevented and also suggests how genes are freed from this silencing in order for normal embryonic development to proceed. As if this were not enough, the researchers have made a beautiful video showing the complex processes occurring in the system of these >22,000 genes, narrated by study leader Sarah Elderkin. Go ahead, take a journey into the fascinating gene galaxy.