{"doi":"10.1242/dev.129.13.3115","title":"Hox repression of a target gene: extradenticle-independent, additive action through multiple monomer binding sites","abstract":"<jats:p>Homeotic (Hox) genes regulate the identity of structures along the anterior-posterior axis of most animals. The low DNA-binding specificities of Hox proteins have raised the question of how these transcription factors selectively regulate target gene expression. The discovery that the Extradenticle (Exd)/Pbx and Homothorax (Hth)/Meis proteins act as cofactors for several Hox proteins has advanced the view that interactions with cofactors are critical to the target selectivity of Hox proteins. It is not clear, however, to what extent Hox proteins also regulate target genes in the absence of cofactors. In Drosophila melanogaster, the Hox protein Ultrabithorax (Ubx) promotes haltere development and suppresses wing development by selectively repressing many genes of the wing-patterning hierarchy, and this activity requires neither Exd nor Hth function. Here, we show that Ubx directly regulates a flight appendage-specific cis-regulatory element of the spalt (sal) gene. We find that multiple monomer Ubx-binding sites are required to completely repress this cis-element in the haltere, and that individual Ubx-binding sites are sufficient to mediate its partial repression. These results suggest that Hox proteins can directly regulate target genes in the absence of the cofactor Extradenticle. We propose that the regulation of some Hox target genes evolves via the accumulation of multiple Hox monomer binding sites. Furthermore, because the development and morphological diversity of the distal parts of most arthropod and vertebrate appendages involve Hox, but not Exd/Pbx or Hth/Meis proteins, this mode of target gene regulation appears to be important for distal appendage development and the evolution of appendage diversity.</jats:p>","journal":"Development","year":2002,"id":14796,"datarank":8.730973871619376,"base_score":5.236441962829949,"endowment":5.236441962829949,"self_citation_contribution":0.7854662944244925,"citation_network_contribution":7.945507577194884,"self_endowment_contribution":0.7854662944244925,"citer_contribution":7.945507577194884,"corpus_percentile":null,"corpus_rank":null,"citation_count":187,"citer_count":181,"citers_with_citation_signal":160,"citers_with_endowment":160,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":115373,"name":"Christopher M. Walsh","orcid":null,"position":1,"is_corresponding":false},{"id":115374,"name":"Sean B. Carroll","orcid":null,"position":2,"is_corresponding":false},{"id":115372,"name":"Ron Galant","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.236441962829949,"endowment":5.236441962829949,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12070087","pmcid":null,"openalex_id":"https://openalex.org/W1864981694","authors":[],"funders":[],"total_grants":0,"fwci":4.0255,"citation_percentile":0.94413106,"influential_citations":0,"citation_trend":[{"year":2012,"count":3},{"year":2013,"count":12},{"year":2014,"count":7},{"year":2015,"count":6},{"year":2016,"count":14},{"year":2017,"count":6},{"year":2018,"count":3},{"year":2019,"count":4},{"year":2020,"count":3},{"year":2021,"count":6},{"year":2022,"count":9},{"year":2023,"count":3},{"year":2024,"count":3},{"year":2025,"count":5}],"oa_status":"closed","license":null,"oa_locations":[{"url":"http://journals.biologists.com/dev/article-pdf/129/13/3115/1140686/3115.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1242/dev.129.13.3115","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12070087","host_type":"repository"},{"url":"http://dev.biologists.org/cgi/content/short/129/13/3115","host_type":"repository"}],"fields_of_study":["Developmental Biology and Gene Regulation","Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities","Neurobiology and Insect Physiology Research","Animals","Binding Sites","DNA-Binding Proteins","Drosophila Proteins","Drosophila melanogaster","Embryo, Nonmammalian","Evolution, Molecular","Gene Expression Regulation, Developmental","Homeodomain Proteins","Insect Proteins","Mutation","Nuclear Proteins","Regulatory Sequences, Nucleic Acid","Serum Response Factor","Transcription Factors","Wings, Animal"],"mesh_terms":["Animals","Binding Sites","DNA-Binding Proteins","Drosophila melanogaster","Embryo, Nonmammalian","Mutation","Nuclear Proteins","Regulatory Sequences, Nucleic Acid","Transcription Factors","Wings, Animal","Homeodomain Proteins","Gene Expression Regulation, Developmental","Evolution, Molecular","Insect Proteins","Serum Response Factor","Drosophila Proteins"],"keywords":["Ultrabithorax","Hox gene","Homeotic gene","Biology","Transcription factor","Decapentaplegic","Genetics","Gene","Homeobox","Antennapedia","Drosophila melanogaster","Psychological repression","Cell biology","Enhancer","Gene expression"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-01T14:41:39.689143Z","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,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}