One particular protein lies at the heart of brain development. A master regulator of gene expression, it's abundantly present in neurons, and its dysfunction underlies Rett syndrome, a neurological disorder that could lead to severe cognitive, motor, and communication impairments in young girls. Yet scientists understand little about how this essential protein does its crucial work at the molecular level.
"People have been studying this protein for decades without a clear consensus on what it is doing, where it binds to the genome, and what its functions are," says Rockefeller's Shixin Liu. Now, a new study from Liu's laboratory sheds light on how the protein, MeCP2, interacts with DNA and chromatin. The findings, published in Nature Structural & Molecular Biology , provide insight into this master regulator, and could open up new avenues for Rett syndrome therapies.
A single-molecule approach MeCP2 is a baffling protein. While it has been implicated in the regulation of thousands of genes and is thought to be central to neurodevelopment, its impacts on the genome are tricky to pin down. Insufficient amounts of wildtype MeCP2 causes Rett syndrome, but too much of the protein causes a similarly debilitating neurological disorder known as MeCP2 duplication syndrome.
Liu and colleagues leveraged the lab's area of expertise—single-molecule observation and manipulation—to better understand how MeCP2 interacts with DNA. The team tethered a single piece of DNA between micron-siz.