{"doi":"10.7554/elife.99394","title":"Genome-wide analysis of Smad and Schnurri transcription factors in C. elegans demonstrates widespread interaction and a function in collagen secretion","abstract":"Smads and their transcription factor partners mediate the transcriptional responses of target cells to secreted ligands of the transforming growth factor-β (TGF-β) family, including those of the conserved bone morphogenetic protein (BMP) family, yet only a small number of direct target genes have been well characterized. In C. elegans, the BMP2/4 ortholog DBL-1 regulates multiple biological functions, including body size, via a canonical receptor-Smad signaling cascade. Here, we identify functional binding sites for SMA-3/Smad and its transcriptional partner SMA-9/Schnurri based on ChIP-seq peaks (identified by modEncode) and expression differences of nearby genes identified from RNA-seq analysis of corresponding mutants. We found that SMA-3 and SMA-9 have both overlapping and unique target genes. At a genome-wide scale, SMA-3/Smad acts as a transcriptional activator, whereas SMA-9/Schnurri direct targets include both activated and repressed genes. Mutations in sma-9 partially suppress the small body size phenotype of sma-3, suggesting some level of antagonism between these factors and challenging the prevailing model for Schnurri function. Functional analysis of target genes revealed a novel role in body size for genes involved in one-carbon metabolism and in the endoplasmic reticulum (ER) secretory pathway, including the disulfide reductase dpy-11 . Our findings indicate that Smads and SMA-9/Schnurri have previously unappreciated complex genetic and genomic regulatory interactions that in turn regulate the secretion of extracellular components like collagen into the cuticle to mediate body size regulation.","journal":"eLife","year":2024,"id":488853,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE266398","GSM8246389","GSM8246390","GSM8246391","GSM8246392","GSM8246393","GSM8246394","GSM8246395","GSM8246396","GSM8246397"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":355386,"name":"Jonathan Dietz","orcid":"0000-0002-4951-6126","position":1,"is_corresponding":false},{"id":1172238,"name":"Zachary Wing","orcid":null,"position":2,"is_corresponding":false},{"id":1333771,"name":"Karen George","orcid":null,"position":3,"is_corresponding":false},{"id":1333772,"name":"Jun Kelly Liu","orcid":null,"position":4,"is_corresponding":false},{"id":526647,"name":"Christopher Rongo","orcid":"0000-0002-1361-5288","position":5,"is_corresponding":false},{"id":397828,"name":"Cathy Savage‐Dunn","orcid":"0000-0002-3457-0509","position":6,"is_corresponding":false},{"id":756913,"name":"Mehul Vora","orcid":"0000-0002-1239-6458","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T02:08:19.655720Z","pmid":"39887187","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":[]}