An interdisciplinary research team of scientists began exploring the three-dimensional organization of the genome plays a key role in gene expression and consequently in determining cell fate. The study findings were published in the Nature Genetics
The model that the 4D Genome team used was cell reprogramming, a process that allows the scientists to revert white blood cells back to a state of pluripotency whereby these cells can differentiate into any other cell type.
Proteins that control gene activity (known as transcription factors) play a key role in this process, which the 4D Genome team studied in great detail, assessing how they induce changes in gene expression, modifications of chromatin and changes in the 3D organization of the genome .
Ralph Stadhouders, co-first author of the paper explained, "We expected that transcription factors would first switch on certain genes, which then afterwards may force a re-organization of the 3D structure of the chromosome ." Surprisingly, what we found is that in a large proportion of the genome, the transcription factors were actually promoting this re-organization before the genes were switched on. "
The machinery required to achieve this selective information resides primarily in so called 'transcription factors' , molecules that switch genes on or off. Many other molecules are also involved in this process, including epigenetic regulators that help to densely pack the genome into the nucleus of a cell, or locally unpack it to allow gene expression.
The scientists used a reprogramming method discovered by CRG senior researcher Thomas Graf and his team. With this precision tool in hand, they were able to study the dynamics of genome organization by comparing the changes in genome architecture and transcription at different times during reprogramming.
"Our paper shows that transcription factors may play to completely new role in cell reprogramming: they do not only switch genes on and off, but also promote the necessary changes to modify the gene expression," states Thomas Graf, lead researcher of this study.
"It May Have Relevant Implications for Researchers worldwide studying gene regulation In general since we know that the large-scale organization of the genome can not be ignored It Also raises new questions About how these large changes can be Brought about: possibly new Mechanisms , perhaps even new machineries that are necessary to change certain areas of the genome "reflects Graf.
The perfect combination: risky + interdisciplinary fundamental science
The findings indicate that genome architecture has important informational value for controlling gene expression during cell reprogramming, and is required for the specialized functions of a cell. "We are only scratching the surface of what could be critical as yet unrecognized mechanisms by which cells regulate gene expression" said co-principal investigator Marc A. Martí-Renom.
In conclusion: The new discovery might also be fundamental for development and for some development-related diseases and cancer . Again, this is an example on how risky science with innovative and interdisciplinary approaches leads to surprising and relevant results to advance knowledge.