{"doi":"10.1210/endocr/bqab237","title":"Concordant Androgen-Regulated Expression of Divergent<i>Rhox5</i>Promoters in Sertoli Cells","abstract":"Concordant transcriptional regulation can generate multiple gene products that collaborate to achieve a common goal. Here we report a case of concordant transcriptional regulation that instead drives a single protein to be produced in the same cell type from divergent promoters. This gene product-the RHOX5 homeobox transcription factor-is translated from 2 different mRNAs with different 5' untranslated regions (UTRs) transcribed from alternative promoters. Despite the fact that these 2 promoters-the proximal promoter (Pp) and the distal promoter (Pd)-exhibit different patterns of tissue-specific activity, share no obvious sequence identity, and depend on distinct transcription factors for expression, they exhibit a remarkably similar expression pattern in the testes. In particular, both depend on androgen signaling for expression in the testes, where they are specifically expressed in Sertoli cells and have a similar stage-specific expression pattern during the seminiferous epithelial cycle. We report evidence for 3 mechanisms that collaborate to drive concordant Pp/Pd expression. First, both promoters have an intrinsic ability to respond to androgen receptor and androgen. Second, the Pp acts as an enhancer to promote androgen-dependent transcription from the Pd. Third, Pd transcription is positively autoregulated by the RHOX5 protein, which is first produced developmentally from the Pp. Together, our data support a model in which the Rhox5 homeobox gene evolved multiple mechanisms to activate both of its promoters in Sertoli cells to produce Rhox5 in an androgen-dependent manner during different phases of spermatogenesis.","journal":"Endocrinology","year":2021,"id":208999,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":796183,"name":"Abhishek Sohni","orcid":"0000-0002-1512-5872","position":1,"is_corresponding":false},{"id":796631,"name":"Chih‐Hong Lou","orcid":null,"position":2,"is_corresponding":false},{"id":796632,"name":"Karel De Gendt","orcid":null,"position":3,"is_corresponding":false},{"id":796633,"name":"Fanmao Zhang","orcid":null,"position":4,"is_corresponding":false},{"id":796184,"name":"EunAh Kim","orcid":"0000-0003-4026-3502","position":5,"is_corresponding":false},{"id":796185,"name":"Panneerdoss Subbarayalu","orcid":"0000-0002-9028-7193","position":6,"is_corresponding":false},{"id":796634,"name":"Waikin Chan","orcid":null,"position":7,"is_corresponding":false},{"id":796635,"name":"Stefanie Kerkhofs","orcid":null,"position":8,"is_corresponding":false},{"id":38576,"name":"Frank Claessens","orcid":"0000-0002-8676-7709","position":9,"is_corresponding":false},{"id":672041,"name":"Sarah Kimmins","orcid":"0000-0002-0168-7233","position":10,"is_corresponding":false},{"id":640937,"name":"Manjeet K. Rao","orcid":"0000-0001-7573-2677","position":11,"is_corresponding":false},{"id":485414,"name":"Marvin L. Meistrich","orcid":"0000-0002-2857-639X","position":12,"is_corresponding":false},{"id":266968,"name":"Miles Wilkinson","orcid":"0000-0002-6416-3058","position":13,"is_corresponding":false},{"id":796182,"name":"Anjana Bhardwaj","orcid":"0000-0003-4234-0241","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-18T23:52:01.526969Z","pmid":"34902009","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":[]}