How unravelling the mysteries of gene expression can help treat cancer
An unexpected finding by a team working in our Department of Biochemistry sheds new light on the mechanisms of gene expression and offers new possibilities for cancer-targeting drugs. The team, led by Professor John Schwabe, looked at bio-molecular complexes as part of an ongoing research effort funded by a £1.4 million grant from The Wellcome Trust. Their findings represent a breakthrough in understanding how genes are decoded from DNA and expressed, and are published in the scientific journal Nature.
Genes lie dormant on DNA sequences until they are expressed or 'activated' by copying them onto smaller RNA strands, in a process called transcription. Because DNA molecules are so long, they are stored in cells in tightly wound-up bundles. Many genes cannot be expressed without 'loosening' these DNA bundles and freeing up the sections of DNA required. A protein called acetyl binds to the bundle and loosens the DNA; a type of enzyme called a histone deacetylase acts to remove acetyls, effectively locking down the DNA bundles and preventing the expression of certain genes. This process is called transcriptional repression or gene silencing: it prevents genes from being activated.
Professor Schwabe's team have discovered an unexpected link between histone deacetylase and inositol phosphate signalling (specifically, IP4) - previously thought to be unrelated. They found that IP4 molecules regulate histone deacetylase enzymes and hence gene silencing. The results are important because cancerous tumours often make use of histone deacetylase to block the expression of genes that would otherwise lead to cancer cell death. Drugs that use IP4 to target histone deacetylase and 'unlock' these cancer-fighting genes could present a new avenue of treatment for cancer.