The FOXA1 protein targets genes to turn them on even if they are hidden away in remote corners of the nucleus of the cell. To do so FOXA1 uses a butterfly-shaped molecular architecture that is able to bind specific sequences of DNA. FOXA1 is important in the formation, correct maintenance of many cell and tissue types including the gut, liver, breast and prostate.
Tumours can form if the balance of FOXA1’s regulatory orchestra is disturbed. A team led by Xuecong Wang of the laboratory of Ralf Jauch at the Guangzhou Institute of Biomedicine and Health discovered a new mechanism for the gene regulation by FOXA1(link). They found that FOXA1 uses a special kind of DNA sequence to pair with itself. This way FOXA1 is able to access an important set of genes and determines whether or not they are available for cellular work or rest in compact nuclear structures.
Peculiarly, this pairing appears to occur even without the two partnering FOXA1 molecules touching each other but indirectly communicate through the newly discovered DNA sequence signature. Mutations that are found in patients suffering from osteoporosis, Parkinson’s disease or breast cancer can perturb this intricate regulatory mesh. The GIBH team worked with scientist of the Max Planck Institute of Molecular Biomedicine, the Broad Institute and the Genome Institute of Singapore for these findings.