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Date: 29/01/2016

Remote uncontrol of DNA in cancer: genome ''wormholes''


How genes are controlled? The traditional view is that genes (our DNA sequences that originate proteins, the building blocks of our cells) are regulated and monitored from a nearby region of the genome called "promoter." We can imagine it as the closest way to regulate point A to point B drawn on white paper: a straight line, and actually this close and direct control of gene expression occurs. But since few years ago began to know that there is a “distance” gene control, such as remote control. That is to get from point A to B does not draw a straight line, but we turned the paper over himself and now the point A is located on point B. This concept would be similar to the astrophysicist concept of "wormholes" ("Wormholes"): two planets seem very far in a straight line but in a three-dimensional universe one could be above the other and be in closer reality. An article published in Genome Biology directed by Dr. Manel Esteller, director of the Epigenetics and Cancer Biology Program of the Bellvitge Biomedical Research Institute (IDIBELL), ICREA researcher and Professor of Genetics at the University of Barcelona, shows that cells tumor have largely lost the ability to perform these remote controls of the genes ("wormholes" of the genome) due to the presence of chemical modifications: epigenetic changes.

 

"We found that a class of distant regulatory regions of genes, called Super-Enhancers, presents changes in the levels of DNA methylation, the most important chemical signature of our genome." -says Dr. Manel Esteller, director of the study- "This alteration causes the control sequences cannot be folded over and regulate genes, activating genes that promote growth and inactivating genes that inhibit it. Discoveries like this and those from other colleagues make us think that it will be too hard to think about genes in terms of linear and static, and instead have to think of them as part of a dynamic network, like pieces of a 3D puzzle 3D."-concludes Dr. Esteller.

 

 

Paper:

 

Heyn H, Vidal E, Ferreira HJ, Vizoso M, Sayols S, Gomez A, Moran S, Boque-Sastre R, Guil S, Martinez-Cardus A, Lin CY, Royo R, Sanchez-Mut JV, Martinez R, Gut M,  Torrents D, Orozco M, Gut I, Young RA, Esteller M. Epigenomic analysis detects aberrant super-enhancer DNA methylation in human cancer.

Genome Biology, 2016.





foto Genomic regions isolated from each other in a straight line, may actually be very close in the three dimensional cell context. The sequences called Super-Enhancer (here shown as a golden ring) perform this function of spatial approach
Genomic regions isolated from each other in a straight line, may actually be very close in the three dimensional cell context. The sequences called Super-Enhancer (here shown as a golden ring) perform this function of spatial approach

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© 2016 Institut d'Investigació Biomèdica de Bellvitge



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