{"doi":"10.1016/j.celrep.2023.112665","title":"ETV2 primes hematoendothelial gene enhancers prior to hematoendothelial fate commitment","abstract":"Mechanisms underlying distinct specification, commitment, and differentiation phases of cell fate determination remain undefined due to difficulties capturing these processes. Here, we interrogate the activity of ETV2, a transcription factor necessary and sufficient for hematoendothelial differentiation, within isolated fate intermediates. We observe transcriptional upregulation of Etv2 and opening of ETV2-binding sites, indicating new ETV2 binding, in a common cardiac-hematoendothelial progenitor population. Accessible ETV2-binding sites are active at the Etv2 locus but not at other hematoendothelial regulator genes. Hematoendothelial commitment coincides with the activation of a small repertoire of previously accessible ETV2-binding sites at hematoendothelial regulators. Hematoendothelial differentiation accompanies activation of a large repertoire of new ETV2-binding sites and upregulation of hematopoietic and endothelial gene regulatory networks. This work distinguishes specification, commitment, and sublineage differentiation phases of ETV2-dependent transcription and suggests that the shift from ETV2 binding to ETV2-bound enhancer activation, not ETV2 binding to target enhancers, drives hematoendothelial fate commitment.","journal":"Cell Reports","year":2023,"id":344540,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1082972,"name":"Chul Kim","orcid":"0000-0001-5032-380X","position":1,"is_corresponding":false},{"id":818925,"name":"Megan Rowton","orcid":"0000-0003-4248-7817","position":2,"is_corresponding":false},{"id":296958,"name":"Rangarajan D. Nadadur","orcid":null,"position":3,"is_corresponding":false},{"id":512505,"name":"Zhezhen Wang","orcid":"0000-0002-4505-4673","position":4,"is_corresponding":false},{"id":876423,"name":"Matthew Stocker","orcid":"0009-0009-5330-8854","position":5,"is_corresponding":false},{"id":297919,"name":"Andrew D. Hoffmann","orcid":"0000-0002-5479-944X","position":6,"is_corresponding":false},{"id":821128,"name":"Erika Hanson","orcid":null,"position":7,"is_corresponding":false},{"id":563465,"name":"Junghun Kweon","orcid":"0000-0002-7538-7663","position":8,"is_corresponding":false},{"id":316846,"name":"Tanvi Sinha","orcid":"0000-0001-9509-5687","position":9,"is_corresponding":false},{"id":297330,"name":"Kyunghee Choi","orcid":"0000-0002-9634-9375","position":10,"is_corresponding":false},{"id":316851,"name":"Brian L. Black","orcid":"0000-0002-6664-8913","position":11,"is_corresponding":false},{"id":820810,"name":"John M. Cunningham","orcid":"0000-0002-6335-5998","position":12,"is_corresponding":false},{"id":270583,"name":"Ivan P. Moskowitz","orcid":"0000-0003-0014-4963","position":13,"is_corresponding":false},{"id":23359,"name":"Kohta Ikegami","orcid":"0000-0002-0405-1193","position":14,"is_corresponding":false},{"id":469568,"name":"Jeffrey D. Steimle","orcid":"0000-0002-1369-9661","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":null,"created_at":"2026-07-19T01:11:30.951510Z","pmid":"37330911","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":[]}