The RNA Pol II Elongation Factor EII3 Marks Enhancers in ES Cells and Primes Future Gene Activation

Enhancers play a central role in precisely regulating the expression of developmentally regulated genes. However, the machineries required for enhancer-promoter communication have remained largely unknown. We have found that EII3, a member of the Ell (eleven-nineteen lysine-rich leukemia gene) family of RNA Pol II elongation factors, occupies enhancers in embryonic stem cells. EII3's association with enhancers is required for setting up proper Pol II occupancy at the promoter-proximal regions of developmentally regulated genes and for the recruitment of the super elongation complex ( SEC) to these loci following differentiation signals. Furthermore, EII3 binding to inactive or poised enhancers is essential for stem cell specification. We have also detected the presence of Pol II and EII3 in germ cell nuclei. These findings raise the possibility that transcription factors could prime gene expression by marking enhancers in ES cells or even as early as in the germ cell state.