Understanding proteins that interpret genome context to stabilise cell states

Animals comprise thousands of different cell types which all contain a complete set of genes. The character of each cell type is determined during differentiation by selecting which genes will be active and which silent. As well as the binary on/off switching of genes, however, the exact levels of each gene product must also be precisely controlled. We found that there are proteins that can read DNA sequence features to achieve this. Two such proteins, SALL4 and MeCP2, are implicated in stabilising the identity of stem cells and nerve cells, respectively. Despite very different biological outputs, SALL4 and MeCP2 work in fundamentally similar ways, and both proteins are of proven biological and biomedical importance. By studying these examples in molecular detail, we will shed light on the role of DNA sequence characteristics in optimising cell identity and will uncover new approaches with therapeutic potential.