The potentially dangerous genes of a critical enzyme control

You may have heard the fantastic “dark side of my genre”. This poorly studied DNA fraction, known as heterochromatin, forms about half of your genetic material, and scientists now begin to solve the role in your cells.

For more than 50 years, scientists have surprised the genetic material in this “dark DNA”. However, there is an increasing evidence that it is critical to work appropriate to protect the cells in a healthy state. Heterochromatin contains tens of thousands of units of dangerous DNA, known as “transposable elements” (or tes). TES are silently “buried” in normal cells in heterochromatin – but they can “wake up” under many pathological conditions and sometimes jump to our normal genetic code “.

And if this change benefits a cell? How great! Transferable elements have been selected for new purposes through evolutionary history-for example, the gland genes in the immune cells and the genes required to direct the development of placenta and mammal evolution are derived from TES.

However, tes can harm our health. Only in the last few years, scientists have attributed heterochromat weakening to aging, prediction, cancer and autoimmune disease.

“You can think of heterochromatin as a prison for transposable elements, La says La Jolla Institute of Immunology (LJI) Professor Anjana Rao, Ph.D. Nature structural and molecular biology Lock Partners Professor Geoffrey J. Faulkner, Ph.D. University of Queensland, Robert Crawford, Ph.D., Biomodal (formerly Cambridge Epigenetix) and Samuel Myers, Ph.D., LJI Assistant Professor. “When heterochromat loses the normal suppressing function, the test escapes and in parallel the health of the cells decreases.”

The new study reveals a remarkable way for the cells to keep us safely from Tes. The researchers found that they have benefited from the entire protein network to suppress the activity of cells and keep them healthy.

Pew Latin American Ph.D. Adam, former instructor and LJ instructor in LJI, Xiang Li, Ph.D.

“Even the increasing expression of these elements can affect the expression of nearby genes, as we have shown in our new article.” “The abundant expression of transferable elements is a signature of many diseases such as cellular aging, human aging, autoimmune disorders and many types of cancer.”

How do cells control transposable elements under control?

Meet the O-GLCNAC transfer gas (OGT), an enzyme in the heart of many basic cellular functions. According to the new study, OGT is also the choreographer when it comes to suppressing the TES and ensuring that the gene expression works smoothly.

For the new project, researchers followed the fact that OGT interacted with important proteins called TET enzymes discovered by RAO LAB in 2009. TET proteins are part of the complex machines that allow the correct replacement of our DNA in our cells.

TET proteins play a role in the critical cycle of DNA modifications, where they play a role in a process that causes the removal of molecular markers connected to DNA (an event called DNA bunch). The most abundant DNA markers called 5MC and 5hmc are normally associated with transcriptional silence and activation. Researchers have shown that 5MC is associated with “closed” genes, and that the 5HMC, which tet proteins media, is associated with the gene expression “open”.

This “open/closed” epigenetic system gives our cells flexibility to respond to environmental changes and health threats. DNA bundle helps our immune cells to activate if a threat detects.

DNA bunch is normal, but cells also need balance. You cannot have tet proteins that activates every gene at the same time. In normal cells, tet protein activity is limited to genes that should be expressed in that cell type.

In the new study, scientists used Oxford Nanopore sequence technology and other latest ranking techniques to explore where the OGT came. What they use is particularly important and a new technique is called Duet Evoc. This multiomic solution, which provides 6 base genome developed by Biomodal, is necessary to detect both 5MC and 5hmc changes at the same time in the same regions in the genome.

Researchers found that OGT protected cells by restricting the tet activity. This is extremely important to control the expression, because it prevents the transformation of the silence modification of 5hmc in the heterochromat of 5MC into an activating modification.

Without OGT in the rudder, tet proteins accelerate DNA bunch in the wrong places, open too much gene at the same time, normally “buried” in our genetic material.

Next steps to understand cancers, autoimmune disease and more

This finding shows how non -encoding areas of our genome can be activated when the tet functions are changed. The new understanding of the OGT-TET partnership shows that these proteins, mediating signs and expression may greatly affect our cells.

“We think of these elements as completely ‘quiet’, and therefore, as a completely inert, but the truth is that the cells need to make a big and continuous investment to keep Tes silent,” he says.

This new research may also be important for future drug development. Scientists have described a large number of cancer -related genes, but controlling their statements continues to be a challenge. New findings show that we can stop cancer growth in interesting new ways, such as restricting the activity of cancer cells.

“We want to control this event, and now we may have an option through OGT and Tets,” Sepulveda says.

RAO emphasizes how OGT controls DNA modifications and teppressions and how the irregularity of this mechanism contributes to autoimmune disorders, cancers and other diseases.

Additional authors of the study, “OGT prevents DNA bunch and prints the expression of transposable elements in heterochrome by restricting the tet activity genome”, Leo J. Arteaga-Vazquez, Isaac F. López-Moyado, Melina Bruina Brunelli, J. Dong, Nasha Jansz, Fabio Pudio Puddu, Aurélie Modat, Jamie Scotcher, Páidí Creed, Patrick Kennedy and Cindy Manriquez.