A study published in the journal Molecular Cell shows, using state-of-the-art microscopy, that the process that copies DNA into RNA, known as transcription, indirectly alters the architecture of the genome. The research has been carried out by an international team led by the Center for Genomic Regulation (CRG) and the University of Pennsylvania (USA).
The authors have found that transcription generates a force, called supercoiling, which makes structural proteins like cohesin glide over the DNA strands. This causes a change in the structure of the genetic material and transforms the three-dimensional organization of the genome.
“The transcription advances through the DNA and opens its strands transiently. This separation is generating the supercoiling. It’s like when you separate the strands of a braided rope and the rope wraps around itself. Transcription, through supercoiling, regulates the three-dimensional organization of DNA ”, the CRG researcher and lead author of the study explained to SINC Vicky neguembor.
Transcription compacts the genome in an indirect but efficient way, helping different regions of the genome to communicate with each other
According to the team, the discovery of this new force may have future implications for the understanding of genetic diseases such as Cornelia de Lange syndrome, caused by mutations in genes encoding cohesins or cohesin regulators. The findings may also help to better understand developmental disorders related to DNA folding, as well as open up new avenues in the investigation of genome fragility and cancer development.
“Our genome it is like a huge instruction manual or like a library. If the information is not well organized in space, it becomes inaccessible for each type of cell to ‘read’ the chapters / books it needs to perform its function. This is obvious, but what we observe is that also the reader or the librarian (in this case, the transcription) contributes to creating that order in space ”, adds the expert.
Chromatin loops, essential for transcription
Supercoiling allows two meters of DNA to be condensed into a tiny space in each human cell. In that condensed state, the genetic material – also known as chromatin– it contains many loops that link different regions of the genome, which would normally be widely separated.
This physical proximity is very important for transcribing DNA into RNA which, in turn, will form proteins. Therefore, chromatin loops are a fundamental biological mechanism for human health and disease.
“The chromatin loop it is what allows individual cells to turn different information on and off. So, for example, a neuron or a muscle cell with the same genomic information behaves in such a different way. The loops are also one of the ways in which the genome compacts itself to fit into the nucleus, ”he explains. Neguembor.
Our genome is like a huge instruction manual or like a library. If the information is not well organized in space, it becomes inaccessible for each type of cell to ‘read’ the chapters or books it needs to perform its function.
“The biological process of transcription has an additional role beyond its fundamental task of creating RNA that eventually becomes proteins. Transcription compacts the genome in an indirect but efficient way, which helps different regions of the genome communicate with each other ”, adds the author.
In order to study the actual shape of the DNA loops, the team used a special type of microscopy which uses high-powered lasers under specific chemical conditions to track the flicker of fluorescent molecules. Thanks to this technique, which is ten times more powerful than conventional microscopy, the researchers were able to identify the loops and cohesins that hold the structure together within cells.
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