{"doi":"10.1101/2020.02.19.956565","title":"Sox17 and β-catenin co-occupy Wnt-responsive enhancers to govern the endodermal gene regulatory network","abstract":"ABSTRACT Lineage specification is governed by gene regulatory networks (GRNs) that integrate the activity of signaling effectors and transcription factors (TFs) on enhancers. Sox17 is a key transcriptional regulator of definitive endoderm development, and yet, its genomic targets remain largely uncharacterized. Here, using genomic approaches and epistasis experiments, we define the Sox17-governed endoderm GRN in Xenopus gastrulae. We show that Sox17 functionally interacts with the canonical Wnt pathway to specify and pattern the endoderm while repressing alternative mesectoderm fates. Sox17 and β-catenin co-occupy hundreds of key enhancers. In some cases, Sox17 and β-catenin synergistically activate transcription independent of Tcfs, whereas on other enhancers, Sox17 represses ß-catenin/Tcf-mediated transcription to spatially restrict gene expression domains. Our findings establish Sox17 as a tissue-specific modifier of Wnt responses and point to a novel paradigm where genomic specificity of Wnt/ß-catenin transcription is determined through functional interactions between lineage-specific Sox TFs and ß-catenin/Tcf transcriptional complexes. Given the ubiquitous nature of Sox TFs and Wnt signaling, this mechanism has important implications across a diverse range of developmental and disease contexts. Key findings Sox17 regulates germ layer segregation by promoting endoderm differentiation while simultaneously repressing mesectoderm fates. Functional interactions between Sox17 and canonical Wnt-signaling is a major feature of the GRN controlling endoderm specification and patterning. Sox17 and β-catenin co-occupy a subset of enhancers to synergistically stimulate transcription in the absence of Tcfs. Sox17 regulates the spatial expression domains of Wnt/β-catenin-responsive transcription in the gastrula.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":121970,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":247683,"name":"Praneet Chaturvedi","orcid":"0000-0002-8713-6570","position":1,"is_corresponding":false},{"id":562195,"name":"Scott A. Rankin","orcid":"0000-0003-3953-6016","position":2,"is_corresponding":false},{"id":562196,"name":"Margaret B. Fish","orcid":"0000-0002-0995-7226","position":3,"is_corresponding":false},{"id":348409,"name":"Marcin Wlizla","orcid":"0000-0001-7328-0734","position":4,"is_corresponding":false},{"id":398243,"name":"Kitt Paraiso","orcid":"0000-0002-6489-810X","position":5,"is_corresponding":false},{"id":562680,"name":"Melissa MacDonald","orcid":null,"position":6,"is_corresponding":false},{"id":229081,"name":"Xiaoting Chen","orcid":"0000-0002-3782-3962","position":7,"is_corresponding":false},{"id":19923,"name":"Matthew T. Weirauch","orcid":"0000-0001-7977-9122","position":8,"is_corresponding":false},{"id":398244,"name":"Ira L. Blitz","orcid":"0000-0002-0173-3287","position":9,"is_corresponding":false},{"id":562681,"name":"Ken W. Y. Cho","orcid":null,"position":10,"is_corresponding":false},{"id":247690,"name":"Aaron M. Zorn","orcid":"0000-0003-3217-3590","position":11,"is_corresponding":false},{"id":562194,"name":"Shreyasi Mukherjee","orcid":"0000-0003-0694-024X","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-18T23:14:46.979435Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}