Wouter de Laat was one of the developers of 4C, a technique highly used to find out DNA interactions between different regions within or between chromosomes. He came from the Hubrecht Institute in Utrecht, The Netherlands, to give a talk to the PRBB today, invited by Guillaume Filion, from the CRG.
The room was packed, with more than 70 researchers ready to learn about how much function is actually within the genome structure. We learned about ‘gene kissing’ – or how genes functionally related but far away in a chromosome come close together during transcription. Interestingly, when de Laat and colleagues inhibited transcription, these interactions (kisses) did not change. The same happened when transcription was overexpressed; and even when they forced mono-allelic expression (silencing just one of the two alleles for a specific gene) and checked by allele-specific 4C, they saw that the contacts with the rest of the chromosome still had not changed.
He used a good metaphor to explain how these 3D localisation in the nucleus takes place: each gene in a chromosome is like a “dog-on-a-leash” – the gene goes wherever the chromosome goes (in space), as the dog does with its owner, although once in that location, a gene is ‘free’ to interact with whoever they want – choose which tree they want to pee on, so to speak. However, there are some genes (mostly largely repetitive regions, such as rRNA genes or centromeres) which are able to decide their preferred location and actually bring the rest of the chromosome: these would be the Pit Bulls amongst the genes.
He talked about much more his lab is studying, mostly comparing the 3D spatial organization of differentiated cells versus embryonic cells (both ESC and IPs), and showed that differentiated cells are also more spatially defined than totipotent cells.
De Laat talked about other uses of 4C, and amongst others he mentioned, at the end of his talk, how he is taking this technique further and using it in diagnostics. Indeed, he has co-founded a company called Cergentis that uses 4C to identify DNA regions which are rearranged.
A report by Maruxa Martinez, Scientific Editor at the PRBB