The H3K27M oncogenic histone mutation drives around 80% of incurable childhood brain tumours known as diffuse midline gliomas (DMGs). Alan Jiao and researchers in Professor Yang Shi’s research group show that the enzyme ubc-20 is the major enzyme responsible for generating di-ubiquinated histone H2B. These results reveal a previously unstudied ubiquitination pathway as a potential novel therapeutic target in incurable paediatric gliomas.
By isolating various H3K27M suppressor mutations, all of which at least partially restore H3K27Me, the global loss of H3K27 tri-methylation. Most of the suppressors mapped to the same histone H3.3 gene, in which the K27M mutation was originally introduced and are predicted to impair PRC2-nucleosome interactions. The group further mapped a single extragenic suppressor to ubc-20 and demonstrated its role as the major enzyme responsible for generating di-ubiquinated histone H2B.
To learn more about this work, please read the full article in PNAS.