Mechanistic Dissection of Tcf7l1-Dependent Enhancer Decommissioning During Exit from Naïve Pluripotency

The transition out of naïve pluripotency requires the simultaneous dissolution of the naïve gene regulatory network as well as a redirection of transcriptional response to Wnt/β-catenin signaling. 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.

Author dc:creator

• Jieun Kwon (5006366)

• Developmental biology
• Stem cell biology
• Epigenetics
• Genomics

Statement dc:rights

• In Copyright
• Open Access after 2028-05-01

DOI dc:identifier

https://doi.org/10.25417/uic.32995013.v1

OAI identifier oai:identifier

oai:figshare.com:article/32995013