SRA

It has become increasingly clear that proper cellular control of pluripotency and differentiation is related to the regulation of rRNA synthesis. To further our understanding of the role that the regulation of rRNA synthesis has on pluripotency we monitored the reduction of rRNA synthesis after the induction of endoderm-specific gene expression in human embryonic stem cells (hESCs) using a brief Activin A treatment. We discovered that the reduction in rRNA synthesis during directed differentiation is rapid (within 6 hours of Activin A treatment), correlates with a reduction in the binding of UBTF, and precedes heterochromatin formation throughout the rRNA gene. The loss of pluripotency and the induction of lineage specific gene expression markers can be induced by reducing rRNA synthesis directly with the Pol I inhibitor, CX-5461. Activin A and CX-5461 both appear to reduce pluripotency and alter lineage-specific transcription, but likely do so via distinct mechanisms. Overall design: UBF Binding by ChIP-seq in untreated and Activin A treated H9 hESCS. mRNA expression level by mRNA-seq in untreated, Activin A treated, and CX-5461 treated H9 hESCs