{"id":{"repo_id":"uic","oai_identifier":"oai:figshare.com:article/32995013"},"canonical_url":"https://search.dev.ndltd.org/etd/uic/oai:figshare.com:article/32995013","repository":{"repo_id":"uic","name":"University of Illinois - Chicago","base_url":"https://api.figshare.com/v2/oai"},"display":{"title":"Mechanistic Dissection of Tcf7l1-Dependent Enhancer Decommissioning During Exit from Naïve Pluripotency","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Jieun Kwon (5006366)"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2026,"date_issued":"2026-05-01T00:00:00Z","date_published":"2026-05-01T00:00:00Z","updated_at":"2026-07-27T21:33:46Z","subjects":["Developmental biology","Stem cell biology","Epigenetics","Genomics"],"languages":[],"rights":["In Copyright","Open Access after 2028-05-01"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://doi.org/10.25417/uic.32995013.v1","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Jieun Kwon (5006366)"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2026-05-01T00:00:00Z"]},{"key":"dc:relation","label":"Dc Relation","values":["https://figshare.com/articles/thesis/Mechanistic_Dissection_of_Tcf7l1-Dependent_Enhancer_Decommissioning_During_Exit_from_Na_ve_Pluripotency/32995013"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Developmental biology","Stem cell biology","Epigenetics","Genomics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["In Copyright","Open Access after 2028-05-01"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["10.25417/uic.32995013.v1"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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."]},{"key":"dc:title","label":"Title","values":["Mechanistic Dissection of Tcf7l1-Dependent Enhancer Decommissioning During Exit from Naïve Pluripotency"]}]}],"canonical_facts":{"dc:creator":["Jieun Kwon (5006366)"],"dc:date":["2026-05-01T00:00:00Z"],"dc:description":["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."],"dc:identifier":["10.25417/uic.32995013.v1"],"dc:relation":["https://figshare.com/articles/thesis/Mechanistic_Dissection_of_Tcf7l1-Dependent_Enhancer_Decommissioning_During_Exit_from_Na_ve_Pluripotency/32995013"],"dc:rights":["In Copyright","Open Access after 2028-05-01"],"dc:subject":["Developmental biology","Stem cell biology","Epigenetics","Genomics"],"dc:title":["Mechanistic Dissection of Tcf7l1-Dependent Enhancer Decommissioning During Exit from Naïve Pluripotency"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T21:33:46Z"}