{"doi":"10.1093/nar/gkaf1015","title":"The homeobox transcription factor MNX1 regulates the expression of many non-MN-specific neuronal genes in motor neurons","abstract":"Motor neurons (MNs) control muscle movement and are essential for breathing, walking and fine motor skills. MN and Pancreas Homeobox 1 (MNX1) has long been recognized as a key marker of the MN lineage, and its deficiency in mice results in early postnatal lethality-likely by causing abnormal MN development and respiratory malfunction. However, its genome-wide targets and regulatory mechanism remain unresolved. Using an in vitro model for efficient MN induction, we identified ∼6000 MNX1-bound loci, of which half are conserved enhancers frequently overlap peaks for core MN-inducing factors ISL1 and LHX3. Despite its widespread binding, Mnx1 knockout affects only a few dozen bound loci and causes mis-regulation of ∼100 genes, the majority are up-regulated neuronal genes which routinely have comparable or even higher expression in brain relative to MNs. Integrative analysis predicts Pbx3 and Pou6f2 as two putative direct targets-both are homeobox genes highly expressed in the central nervous system, and adjacent to MNX1-repressed enhancers according to luciferase reporter assay. Collectively, our results suggest MNX1 restrains the expression of non-MN-specific neuronal genes, likely mainly through an indirect fashion. Further, the rarity of direct targets in contrast to widespread binding reflects a distinctive mode of transcriptional regulation.","journal":"Nucleic Acids Research","year":2025,"id":536892,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9452,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":996397,"name":"Hairui Fan","orcid":"0000-0003-2472-4647","position":1,"is_corresponding":false},{"id":265475,"name":"Sherry Ralls","orcid":null,"position":2,"is_corresponding":false},{"id":75632,"name":"Warren L. Wu","orcid":"0000-0002-1692-3470","position":3,"is_corresponding":false},{"id":808948,"name":"Justin Demmerle","orcid":"0000-0002-4005-1705","position":4,"is_corresponding":false},{"id":809588,"name":"Jiayao Jiang","orcid":null,"position":5,"is_corresponding":false},{"id":567778,"name":"Jinpu Jin","orcid":"0009-0007-9091-0866","position":6,"is_corresponding":false},{"id":322313,"name":"Carson J. Miller","orcid":"0000-0001-5459-7015","position":7,"is_corresponding":false},{"id":264031,"name":"Gernot Wolf","orcid":"0000-0002-3943-8662","position":8,"is_corresponding":false},{"id":258781,"name":"Todd S. Macfarlan","orcid":"0000-0003-2495-9809","position":9,"is_corresponding":false},{"id":264033,"name":"Ming‐an Sun","orcid":"0000-0002-4661-3027","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T02:52:09.056872Z","pmid":"41099694","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":[]}