Regulation of the polycomb repressive complexes by histone reader domains

Every cell in the human body contains the same genomic DNA, containing approximately 20,000 genes, which must give rise to all of the different cell types we have. For example, skin cells and brain cells contain the same genomic DNA, but these cells are vastly different in their structure and function. The different structure and function of these cell types arise from the ability to turn certain genes on and off in a spatial and temporal manner. One way to regulate whether a gene is on or off is the presence of proteins, known as histones, which wrap up our genomic DNA into a fundamental repeating unit known as the nucleosome. These nucleosomes can be modified, moved or removed from DNA by large protein complexes which serves to turn genes on or off. How these protein complexes interact with nucleosomes, which genes containing nucleosomes they go to and how the modify nucleosomes is currently under intense research.

The Polycomb repressive complexes (PRC1 and PRC2) are two protein complexes that are important for turning genes off as precursor cells develop into different cell types. How these protein complexes are brought to certain genes for repression and how they modify chromatin is still an active area of research. My work identifies specific regions of two proteins in the PRC1 and PRC2 that are important for the interaction with the nucleosomes, deciding what genes they go to in the cell and how they affect the complexes ability to modify chromatin. Importantly, these two complexes have been implicated in disease states such as cancer and many others, which have made them highly valuable targets for drug development. Together, my work enhances our knowledge of how these two protein complexes work to repress genes and provides a framework for the development of drugs to treat disease states when there function becomes altered.