Discovery of Two Proteins That Could Enable Safer Cancer Therapies

Researchers at the University of Geneva have uncovered two key proteins—MLF2 and RBM15—that regulate chromatin remodeling, a crucial process in gene expression. Proper gene expression is essential for normal cellular function, as it controls which parts of the DNA are activated at any given time. When gene regulation fails, it can lead to the activation of inappropriate genetic regions, contributing to the development of cancers and neurodevelopmental disorders.

Chromatin, the complex of DNA and proteins within the nucleus, helps organize the vast amount of genetic material in cells by tightly packing the DNA. This condensation makes the DNA inaccessible for reading, so specialized proteins are needed to remodel chromatin, allowing selective access to genetic instructions.

Disruptions in this epigenetic mechanism can cause cells to behave abnormally. For instance, inappropriate exposure of chromatin regions can activate oncogenes, leading to skin cancers, or disturb neuronal development, which might contribute to conditions such as autism. Understanding these processes is vital for developing targeted therapies.

Using the advanced CRISPR-Cas9 gene editing technology, the research team conducted a comprehensive genetic screen analyzing more than 20,000 genes. This approach led to the identification of MLF2 and RBM15 as significant modulators of chromatin remodeling. These proteins influence the activity of the SWI/SNF complex, which is vital for adjusting chromatin structure.

The discovery opens the door to new therapeutic possibilities. By targeting MLF2 and RBM15, scientists hope to develop treatments that can effectively inhibit or modify dysfunctional chromatin remodeling, potentially reducing the toxicity of current cancer therapies and improving their efficacy.

Looking ahead, scientists aim to determine whether manipulating these proteins can selectively kill cancer cells or simply slow their growth. The ultimate goal is to find the most effective molecules to correct chromatin remodeling abnormalities and offer less toxic, more precise cancer treatments.

The findings were published in Nature Communications and represent a significant step forward in understanding gene regulation mechanisms and translating that knowledge into innovative therapies for cancer and other genetic disorders.