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Researchers uncover key player behind gene repression in rare brain tumour

22 May, 2025

Diffuse midline glioma (DMG) is driven by a mutation in a protein called histone H3, which causes widespread disruptions in how genes are turned on and off. 

Although scientists have known that this mutation leads to abnormal gene silencing, exactly how this happens has remained a mystery - until now.

Researchers at the Institute of Genetics and Cancer (IGC) have identified a rare but powerful protein complex that plays a central role in this gene repression. 

The complex, made up of several proteins including CBX4 and PCGF4, belongs to a group of gene-silencing machines called cPRC1. Surprisingly, the CBX4/PCGF4 version makes up less than 5% of these complexes in tumour cells but turns out to be essential for cancer growth.

This specific complex binds to certain areas of DNA and switches off genes that normally help cells mature or stop dividing. By doing this, it helps the tumour cells stay in a primitive, fast-growing state. 

When the researchers disabled CBX4 or PCGF4 in lab-grown DMG cells or mouse models, the tumours stopped growing. Other similar proteins did not have the same effect, showing that this particular complex has a unique role in the disease.

These findings point to a new and highly specific weakness in DMG tumours. Rather than targeting broad systems in the cell, future treatments could focus on disrupting this small but critical protein complex, potentially leading to more effective and safer therapies for children with this devastating cancer.

Source:https://institute-genetics-cancer.ed.ac.uk/researchers-uncover-key-player-behind-gene-repression-in-rare-brain-tumour


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