Reversible 'master switch' for developmental genes discovered

Researchers from Brigham and Women’s Hospital (BWH) have identified a reversible ‘master switch’ on most developmental genes in the common fruit fly, a powerful model organism for studying how human genes are organised and function.

The human genome contains billions of DNA ‘letters’ that can only be read as words, phrases and sentences with the help of proteins that, metaphorically, mark the DNA with punctuation. Together, the DNA-protein combinations form chromatin, which provides the essential annotation for gene transcription.

However, it is still not understood how the annotation and readout of a single genome differs across cell types. The differences are crucial for normal development and are mutated in cancer. Currently, it is thought that different combinations of proteins act at each of the thousands of genes, and deciphering the numerous complex patterns is a difficult task.

Led by principal investigator Mitzi Kuroda, the BWH researchers identified a reversible master switch that sat on potentially all developmental genes in their model organism, the fruit fly. Their bivalent master switch model provides a conceptually simple explanation for how each developmental step is made along the path to different cell types, dependent on cell type-specific proteins, but acting through this common module.

According to the researchers, the fly model is likely to extend and synergise with seminal work by Harvard Medical School Professor Brad Bernstein and colleagues on the regulation of key developmental genes in mammalian embryos. It has been published in the journal Genes & Development.