{"doi":"10.1101/gad.350569.123","title":"Major β cell-specific functions of NKX2.2 are mediated via the NK2-specific domain","abstract":"The consolidation of unambiguous cell fate commitment relies on the ability of transcription factors (TFs) to exert tissue-specific regulation of complex genetic networks. However, the mechanisms by which TFs establish such precise control over gene expression have remained elusive-especially in instances in which a single TF operates in two or more discrete cellular systems. In this study, we demonstrate that β cell-specific functions of NKX2.2 are driven by the highly conserved NK2-specific domain (SD). Mutation of the endogenous NKX2.2 SD prevents the developmental progression of β cell precursors into mature, insulin-expressing β cells, resulting in overt neonatal diabetes. Within the adult β cell, the SD stimulates β cell performance through the activation and repression of a subset of NKX2.2-regulated transcripts critical for β cell function. These irregularities in β cell gene expression may be mediated via SD-contingent interactions with components of chromatin remodelers and the nuclear pore complex. However, in stark contrast to these pancreatic phenotypes, the SD is entirely dispensable for the development of NKX2.2-dependent cell types within the CNS. Together, these results reveal a previously undetermined mechanism through which NKX2.2 directs disparate transcriptional programs in the pancreas versus neuroepithelium.","journal":"Genes & Development","year":2023,"id":389880,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"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":634576,"name":"Joshua A. Levine","orcid":"0000-0003-1112-2700","position":1,"is_corresponding":false},{"id":1161729,"name":"Angela J. Churchill","orcid":null,"position":2,"is_corresponding":false},{"id":1161730,"name":"Bryce Hopwood","orcid":null,"position":3,"is_corresponding":false},{"id":580456,"name":"Cailin Deiter","orcid":"0000-0002-0772-6387","position":4,"is_corresponding":false},{"id":580873,"name":"Michelle A. Guney","orcid":null,"position":5,"is_corresponding":false},{"id":282722,"name":"Kristen L. Wells","orcid":"0000-0002-7466-8164","position":6,"is_corresponding":false},{"id":1161731,"name":"Jessica M. Schrunk","orcid":null,"position":7,"is_corresponding":false},{"id":408578,"name":"Yuchun Guo","orcid":"0000-0003-2357-1546","position":8,"is_corresponding":false},{"id":553848,"name":"Jennifer Hammelman","orcid":"0000-0002-1008-2666","position":9,"is_corresponding":false},{"id":408579,"name":"David K. Gifford","orcid":"0000-0003-1709-4034","position":10,"is_corresponding":false},{"id":289722,"name":"Mark A. Magnuson","orcid":"0000-0002-8824-6499","position":11,"is_corresponding":false},{"id":581378,"name":"Hynek Wichterle","orcid":"0000-0002-7817-0080","position":12,"is_corresponding":false},{"id":449848,"name":"Lori Sussel","orcid":"0000-0003-4672-7304","position":13,"is_corresponding":false},{"id":1161728,"name":"Vladimir Abarinov","orcid":null,"position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T01:18:32.854511Z","pmid":"37364986","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":[]}