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oai:figshare.com:article/32995013 2026-05-01T00:00:00Z portal_693 item_type_8 month_year_05_2026

Mechanistic Dissection of Tcf7l1-Dependent Enhancer Decommissioning During Exit from Naïve Pluripotency Jieun Kwon (5006366) Developmental biology Stem cell biology Epigenetics Genomics 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. 2026-05-01T00:00:00Z Text Thesis 10.25417/uic.32995013.v1 https://figshare.com/articles/thesis/Mechanistic_Dissection_of_Tcf7l1-Dependent_Enhancer_Decommissioning_During_Exit_from_Na_ve_Pluripotency/32995013 In Copyright Open Access after 2028-05-01