Integration of the naïve pluripotency gene network with the response to Gsk3 inhibition by Tcf7l1-driven enhancer decommissioning (Microarray)

Here, we show that Tcf7l1 functions as a linchpin factor that connects the two outcomes via effects at Tcf7l1-bound cis-regulatory elements in mouse pluripotent stem cells. A combination of gene knockout and inducible expression lines of ESC were generated to experimentally isolate effects of Tcf/Lef factors on pluripotency.

Naïve cis-regulatory elements were specifically bound by and rapidly decommissioned by Tcf7l1 upon releasing cells from Gsk3 inhibition. These findings suggest that Tcf7l1-mediated enhancer decommissioning serves as a critical mechanism by which pluripotent cells rapidly alter the response to signaling pathways in preparation for gastrulation, and it may be a mechanism used in diverse cell types for modulating effects of Wnt/β-catenin signaling pathway on cell fate decisions.