{"doi":"10.1093/genetics/iyaf161","title":"Transcriptional control of <i>C. elegans</i> male tail tip morphogenesis by DMD-3","abstract":"Sexually dimorphic morphogenesis is governed by DM-domain transcription factors (TFs) in many animals, but how this transcriptional control links to the morphogenetic mechanisms is insufficiently known. The DM-domain TF DMD-3 in Caenorhabditis elegans is the master regulator of a male-specific morphogenetic event that changes the shape of the tail tip from long and pointed in larvae to short and round in adults. This tail tip morphogenesis (TTM) involves cell-shape changes, cell migration, and fusion. To understand how transcriptional regulation by DMD-3 governs TTM, we used male-specific ChIP-seq to identify its direct targets. We found 1,755 DMD-3-bound sites. We identify a DMD-3-associated binding motif and validate its function in TTM. This motif is similar to the binding motif of EOR-1, and eor-1 mutations affect TTM at a penetrance of 13%. This suggests that DMD-3 may act cooperatively with EOR-1 and possibly other TFs. DMD-3 targets 273 genes that play a role in TTM. These genes include other TFs as well as effectors and components of morphogenetic mechanisms. By deleting DMD-3-bound sites endogenously and observing changes in reporter expression and tail tip phenotypes, we identify tissue-specific enhancers in the cis-regulatory regions of fos-1, pan-1, nmy-2, and hmr-1 that play a role in TTM. For fos-1, we propose that a feed-forward loop is responsible for the tail-tip-specific increase in gene expression. Our study suggests that the gene regulatory network for TTM downstream of DMD-3 involves an unexpectedly large hierarchical cascade of TFs, but DMD-3 directly targets some non-TF genes as well.","journal":"Genetics","year":2025,"id":526509,"datarank":0.21434823137967876,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.006404077211695147,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.006404077211695147,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":2,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE282566"]},"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":23423,"name":"Sevinç Ercan","orcid":"0000-0001-7297-1648","position":1,"is_corresponding":false},{"id":583205,"name":"Karin Kiontke","orcid":"0000-0003-1588-4884","position":2,"is_corresponding":false},{"id":52154,"name":"David Fitch","orcid":"0000-0001-6940-7544","position":3,"is_corresponding":false},{"id":1252589,"name":"Porfirio Fernández","orcid":"0009-0006-7118-6158","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T02:50:30.402772Z","pmid":"40795528","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":[]}