Principal Investigator Laurie Ann Boyer
Polycomb group (PcG) proteins are essential for metazoan development and function in heterochromatic gene silencing by post-translational modification of histone proteins. PcG group proteins have been shown to play key roles in stem cell maintenance in a variety of organisms. Our recent work has shown that PcG proteins control a large cohort of genes with known roles in development in both mouse and human ES cells, whose expression would otherwise promote differentiation and loss of pluripotency. How these epigenetic regulators are targeted to specific genomic sites in ES and how PcG proteins influence chromatin structure to allow for proper control of developmental gene expression programs during differentiation is an important and unresolved question. Evidence in a variety of eukaryotes suggests that the RNAi machinery as well as large noncoding RNAs are necessary for pericentric heterochromatin formation and may play a role in the recruitment of PcG proteins to their target genes. We are particularly interested in investigating a role for RNA molecules in mediating silencing through direct (cis) recruitment of PcG proteins as well as by more indirect long-range (trans) interactions.