Genome-wide analysis of Smad and Schnurri transcription factors in C. elegans demonstrates widespread interaction and a function in collagen secretion
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 be...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2025-01-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/99394 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832576067315957760 |
|---|---|
| author | Mehul Vora Jonathan Dietz Zachary Wing Karen George Jun Kelly Liu Christopher Rongo Cathy Savage-Dunn |
| author_facet | Mehul Vora Jonathan Dietz Zachary Wing Karen George Jun Kelly Liu Christopher Rongo Cathy Savage-Dunn |
| author_sort | Mehul Vora |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b67e5abd407d438cb974d3a0b18a316d |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-b67e5abd407d438cb974d3a0b18a316d2025-01-31T12:45:30ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.99394Genome-wide analysis of Smad and Schnurri transcription factors in C. elegans demonstrates widespread interaction and a function in collagen secretionMehul Vora0Jonathan Dietz1Zachary Wing2Karen George3Jun Kelly Liu4Christopher Rongo5https://orcid.org/0000-0002-1361-5288Cathy Savage-Dunn6https://orcid.org/0000-0002-3457-0509Waksman Institute, Department of Genetics, Rutgers University, New Brunswick, United States; ModOmics Ltd, Southampton, United KingdomWaksman Institute, Department of Genetics, Rutgers University, New Brunswick, United StatesDepartment of Biology, Queens College, CUNY, New York, United StatesWaksman Institute, Department of Genetics, Rutgers University, New Brunswick, United StatesDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, United StatesWaksman Institute, Department of Genetics, Rutgers University, New Brunswick, United StatesDepartment of Biology, Queens College, CUNY, New York, United States; PhD Program in Biology, The Graduate Center, CUNY, New York, United StatesSmads 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.https://elifesciences.org/articles/99394SmadSchnurriBMPcollagenC. elegansbody size |
| spellingShingle | Mehul Vora Jonathan Dietz Zachary Wing Karen George Jun Kelly Liu Christopher Rongo Cathy Savage-Dunn Genome-wide analysis of Smad and Schnurri transcription factors in C. elegans demonstrates widespread interaction and a function in collagen secretion eLife Smad Schnurri BMP collagen C. elegans body size |
| title | Genome-wide analysis of Smad and Schnurri transcription factors in C. elegans demonstrates widespread interaction and a function in collagen secretion |
| title_full | Genome-wide analysis of Smad and Schnurri transcription factors in C. elegans demonstrates widespread interaction and a function in collagen secretion |
| title_fullStr | Genome-wide analysis of Smad and Schnurri transcription factors in C. elegans demonstrates widespread interaction and a function in collagen secretion |
| title_full_unstemmed | Genome-wide analysis of Smad and Schnurri transcription factors in C. elegans demonstrates widespread interaction and a function in collagen secretion |
| title_short | Genome-wide analysis of Smad and Schnurri transcription factors in C. elegans demonstrates widespread interaction and a function in collagen secretion |
| title_sort | genome wide analysis of smad and schnurri transcription factors in c elegans demonstrates widespread interaction and a function in collagen secretion |
| topic | Smad Schnurri BMP collagen C. elegans body size |
| url | https://elifesciences.org/articles/99394 |
| work_keys_str_mv | AT mehulvora genomewideanalysisofsmadandschnurritranscriptionfactorsincelegansdemonstrateswidespreadinteractionandafunctionincollagensecretion AT jonathandietz genomewideanalysisofsmadandschnurritranscriptionfactorsincelegansdemonstrateswidespreadinteractionandafunctionincollagensecretion AT zacharywing genomewideanalysisofsmadandschnurritranscriptionfactorsincelegansdemonstrateswidespreadinteractionandafunctionincollagensecretion AT karengeorge genomewideanalysisofsmadandschnurritranscriptionfactorsincelegansdemonstrateswidespreadinteractionandafunctionincollagensecretion AT junkellyliu genomewideanalysisofsmadandschnurritranscriptionfactorsincelegansdemonstrateswidespreadinteractionandafunctionincollagensecretion AT christopherrongo genomewideanalysisofsmadandschnurritranscriptionfactorsincelegansdemonstrateswidespreadinteractionandafunctionincollagensecretion AT cathysavagedunn genomewideanalysisofsmadandschnurritranscriptionfactorsincelegansdemonstrateswidespreadinteractionandafunctionincollagensecretion |