Immune Health Maintained by Meticulously Ordered DNA

Source: Walter and Eliza Hall Institute

Summary: Researchers have revealed how immune health is maintained by the exquisite organisation skills of a protein called Pax5.

The new study shows how Pax5 helps to efficiently organise the genetic information (DNA) required for our immune cells to maintain their form, function and help fight disease. The findings also suggest that a breakdown in this process of organisation by Pax5 could increase the risk of diseases such as cancer. The researchers had shown, for the first time, that Pax5 could sweep across the genome and fold, twist and store DNA for B cells in a fantastically ordered way making each cell into a jam-packed but very neat suitcase. This immaculate organisation is crucial because each cell contains roughly two meters of DNA – that’s a huge amount of material to fit inside something smaller than a grain of sand. The researchers from the Walter and Eliza Hall Institute have revealed how immune health is maintained by the exquisite organisation skills of a protein called Pax5. The study findings were published in the journal Nature Immunology.


Pax5. Credit: Ms Etsuko Uno, The Walter and Eliza Hall Institute of Medical Research

With the help of powerful computers, the ream performed thousands of complex calculations to spot the difference in DNA organisation when Pax5 was present, versus absent, from the B cells. Their analyses showed that without Pax5, the cells could no longer package their DNA adequately. Bioinformatics is shining a light on how vital factors regulate our DNA. This in turns progresses an understanding of what could be going wrong in cases of a disease. The findings were particularly intriguing because for two decades Pax5 was known only as a ‘transcription factor‘. Transcription factors help cells identify the instructions they need, but there was no evidence they could also play a part in the organisation and upkeep of this information, until now.”

Dr. Allan said the disarray of DNA could lead to errors ‘further down the line’.”Seemingly small errors in the process of DNA organisation can turn out to be very serious drivers for a disease.”

More Information: Timothy M. Johansen et al, “Transcription-factor-mediated supervision of global genome architecture maintains B cell identity”, Nature Immunology (2018). DOI: 10.1038/s41590-018-0234-8 

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