Immune health maintained by a carefully ordered DNA

Researchers at Walter Hall and the Eliza Hall Institute have revealed that the excellent skills in organizing a protein called Pax5 ensure the maintenance of immune health.

The new study published today in Immunology of nature shows how Pax5 helps to efficiently organize the genetic information (DNA) necessary for immune cells to maintain their shape, function and contribute to the fight against diseases. The findings also suggest that a break in this organizational process in Pax5 could increase the risk of diseases such as cancer.

The research was led by Dr. Rhys Allan and Tim Johanson, in collaboration with Professor Stephen Nutt and Professor of Bioinformatics, Gordon Smyth, and Dr. Hannah Coughlan of the Walter and Eliza Hall Medical Research Institute .

The importance of maintaining order

Dr. Johanson stated that the researchers had shown, for the first time, that Pax5 could scan the genome, bend, twist and store B-cell DNA in a fantastic way, transforming each cell into a stuffed suitcase but very neat.

"This immaculate organization is crucial because each cell contains about two meters of DNA, which represents a huge amount of material to be inserted into something smaller than a grain of sand.

"Every second of every day, different cells need to have access to very specific DNA parts to perform a multitude of tasks that help us stay healthy," he said.

Dr. Johanson said that life depends on cells getting what they need, when they need it.

"For example, immune B cells need to have access to the right information to produce potentially vital antibodies that are essential for the vaccine and immune response.

"Think about how a well-ordered suitcase increases your chances of finding a specific piece of clothing at any time, and how a confusing case might prevent you from finding what you need." In the case of our bodies, the difference between the disorder can be a matter of life and death, "he said.

Disorder leads to illness

Dr. Allan said that the disarray of DNA could lead to mistakes "later in the line".

"Apparently minimal errors in the process of organizing DNA can prove to be very serious factors of infection.

"A lack of instructions necessary for the operation may expose the cells to a transformation or transformation into something that they should not perhaps be, for example a cancer cell." so not surprising that Pax5 is defective in many childhood leukemias. "

The power of the computer

Dr. Coughlan said that recent technological advances have allowed teams to visualize for the first time the activity of Pax5 across the genome.

"With the help of powerful computers, we performed thousands of complex calculations to spot the difference in the organization of DNA between the B cells present and absent from Pax5." Our analyzes showed that without Pax5, cells could no longer pack their DNA properly.

"Bioinformatics highlights how vital factors regulate our DNA, which in turn helps to better understand what could go wrong in the event of illness," she said.

Two roles for the same player

Dr. Allan said the results were particularly intriguing because for two decades Pax5 was only known as a "transcription factor".

"Transcription factors help cells identify the instructions they need, but there was no evidence that they could also play a role in organizing and maintaining this information, until now." ", did he declare.

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More information:
Supervision of the global genome architecture via transcription factors maintains the identity of B cells, Immunology of nature (2018). DOI: 10.1038 / s41590-018-0234-8, https://www.nature.com/articles/s41590-018-0234-8