"Gateway to the Trophoblast Epigenome; PcG SFMBT2 and Placenta Development"

The placenta is a transient, but critical, extraembryonic organ required for development of mammals. The cell lineage that produces the various types of placenta cells, trophoblast, is particularly sensitive to genomic imprinting, an epigentic process that marks a small subset of genes for silencing on a parent-of-origin basis. Our lab discovered that the rodent PcG gene Sfmbt2 is imprinted in trophoblast; it is expressed robustly from the paternal allele while the maternal allele is silent. Our experiments have revealed that Sfmbt2 is required to maintain the pool of undifferentiated trophoblast progenitor cells, and that mutants lacking this PcG protein have severely reduced placentas, probably reflecting premature differentiation. We are also investigating the mechanism by which the maternal allele is silenced. There is no dependence on DNA methylation; however, a large block of miRNAs present in mouse and rat genes but absent in other mammals correlates with imprinting of Sfmbt2, suggesting that RNAi biochemistry may drive silencing of the maternal allele. Experiments exploring this idea will be discussed.