Genome-wide analysis of Smad and Schnurri transcription factors inC. elegansdemonstrates widespread interaction and a function in collagen secretion DOI Creative Commons
Mehul Vora, Jonathan Dietz,

Zachary Wing

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 6, 2024

Smads and their transcription factor partners mediate the transcriptional responses of target cells to secreted ligands Transforming Growth Factor-β (TGF-β) family, including those conserved bone morphogenetic protein (BMP) yet only a small number direct genes have been well characterized. In C. elegans, BMP2/4 ortholog DBL-1 regulates multiple biological functions, body size, via canonical receptor-Smad signaling cascade. Here, we identify functional binding sites for SMA-3/Smad its partner SMA-9/Schnurri based on ChIP-seq peaks (identified by modEncode) expression differences nearby identified from RNA-seq analysis corresponding mutants. We found that SMA-3 SMA-9 both overlapping unique genes. At genome-wide scale, acts as activator, whereas targets include activated repressed Mutations in sma-9 partially suppress size phenotype sma-3, suggesting some level antagonism between these factors challenging prevailing model Schnurri function. Functional revealed novel role involved one-carbon metabolism endoplasmic reticulum (ER) secretory pathway, disulfide reductase dpy-11. Our findings indicate previously unappreciated complex genetic genomic regulatory interactions turn regulate secretion extracellular components like collagen into cuticle regulation.

Язык: Английский

TGF-β ligand cross-subfamily interactions in the response of Caenorhabditis elegans to a bacterial pathogen DOI Creative Commons

Emma Jo Ciccarelli,

Zachary Wing,

Moshe Bendelstein

и другие.

PLoS Genetics, Год журнала: 2024, Номер 20(6), С. e1011324 - e1011324

Опубликована: Июнь 14, 2024

The Transforming Growth Factor beta (TGF-β) family consists of numerous secreted peptide growth factors that play significant roles in cell function, tissue patterning, and organismal homeostasis, including wound repair immunity. Typically studied as homodimers, these ligands have the potential to diversify their functions through ligand interactions may enhance, repress, or generate novel functions. In nematode Caenorhabditis elegans , there are only five TGF-β ligands, providing an opportunity dissect fewer combinations than vertebrates. As vertebrates, can be divided into bone morphogenetic protein (BMP) TGF-β/Activin subfamilies predominantly signal discrete signaling pathways. BMP subfamily DBL-1 has been well for its role innate immune response C . Here we show all a survival on bacterial pathogens. We also demonstrate multiple pairs act nonredundantly part this response. two BMP-like ligands–DBL-1 TIG-2–function independently each other response, while TIG-2/BMP TGF-β/Activin-like TIG-3 function together. Structural modeling supports TIG-2 form heterodimers. Additionally, identify members rare subset lacking conserved cysteine responsible disulfide linking mature dimers. Finally, canonical DBL-1/BMP receptor Smad transducers pathogens, components DAF-7 pathway do not major survival. These results interact provide mechanism distinguishing developmental homeostatic from acute such

Язык: Английский

Процитировано

7
Genome-wide analysis of Smad and Schnurri transcription factors in C. elegans demonstrates widespread interaction and a function in collagen secretion DOI Open Access
Mehul Vora, Jonathan Dietz,

Zachary Wing

и другие.

Опубликована: Янв. 2, 2025

Smads and their transcription factor partners mediate the transcriptional responses of target cells to secreted ligands Transforming Growth Factor-β (TGF-β) family, including those conserved bone morphogenetic protein (BMP) yet only a small number direct genes have been well characterized. In C. elegans, BMP2/4 ortholog DBL-1 regulates multiple biological functions, body size, via canonical receptor-Smad signaling cascade. Here, we identify functional binding sites for SMA-3/Smad its partner SMA-9/Schnurri based on ChIP-seq peaks (identified by modEncode) expression differences nearby identified from RNA-seq analysis corresponding mutants. We found that SMA-3 SMA-9 both overlapping unique genes. At genome-wide scale, acts as activator, whereas targets include activated repressed Mutations in sma-9 partially suppress size phenotype sma-3, suggesting some level antagonism between these factors challenging prevailing model Schnurri function. Functional revealed novel role involved one-carbon metabolism endoplasmic reticulum (ER) secretory pathway, disulfide reductase dpy-11. Our findings indicate previously unappreciated complex genetic genomic regulatory interactions turn regulate secretion extracellular components like collagen into cuticle regulation.

Язык: Английский

Процитировано

0
Genome-wide analysis of Smad and Schnurri transcription factors in C. elegans demonstrates widespread interaction and a function in collagen secretion DOI Creative Commons
Mehul Vora, Jonathan Dietz,

Zachary Wing

и другие.

eLife, Год журнала: 2025, Номер 13

Опубликована: Янв. 31, 2025

Smads and their transcription factor partners mediate the transcriptional responses of target cells to secreted ligands transforming growth factor-β (TGF-β) family, including those conserved bone morphogenetic protein (BMP) yet only a small number direct genes have been well characterized. In C. elegans, BMP2/4 ortholog DBL-1 regulates multiple biological functions, body size, via canonical receptor-Smad signaling cascade. Here, we identify functional binding sites for SMA-3/Smad its partner SMA-9/Schnurri based on ChIP-seq peaks (identified by modEncode) expression differences nearby identified from RNA-seq analysis corresponding mutants. We found that SMA-3 SMA-9 both overlapping unique genes. At genome-wide scale, acts as activator, whereas targets include activated repressed Mutations in sma-9 partially suppress size phenotype sma-3, suggesting some level antagonism between these factors challenging prevailing model Schnurri function. Functional revealed novel role involved one-carbon metabolism endoplasmic reticulum (ER) secretory pathway, disulfide reductase dpy-11 . Our findings indicate previously unappreciated complex genetic genomic regulatory interactions turn regulate secretion extracellular components like collagen into cuticle regulation.

Язык: Английский

Процитировано

0
BMP-Dependent Mobilization of Fatty Acid Metabolism Promotes Caenorhabditis elegans Survival on a Bacterial Pathogen DOI Creative Commons
Katerina K. Yamamoto,

Min-Tao Wan,

Rijul S. Penkar

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 15, 2025

The Bone Morphogenetic Proteins (BMPs) are secreted peptide ligands of the Transforming Growth Factor beta (TGF-β) family, initially identified for their roles in development and differentiation across animal species. They now increasingly recognized physiology infectious disease. In nematode Caenorhabditis elegans, BMP ligand DBL-1 controls fat metabolism immune response, addition to its body size regulation development. regulates classical aspects innate immunity, including induction anti-microbial peptides. We theorized that BMP-dependent could also promote resilience against microbial pathogens. found exposure a bacterial pathogen alters total stores, lipid droplet dynamics, gene expression manner. further showed fatty acid desaturation plays major role survival on pathogen, while β-oxidation more minor role. conclude C. elegans mobilizes response survival. Our investigation provides framework study potential metabolic interventions support therapeutics complementary antibiotic strategies.

Язык: Английский

Процитировано

0
Behavioral Cooperation or Conflict of Human Intestinal Roundworms and Microbiomes: A Bio-Activity Perspective DOI Creative Commons
Meisam Khazaei, Malihe Parsasefat, Aisa Bahar

и другие.

Cells, Год журнала: 2025, Номер 14(7), С. 556 - 556

Опубликована: Апрель 7, 2025

Human infections are greatly impacted by intestinal nematodes. These nematodes, which encompass the large roundworms, have a direct impact on human health and well-being due to their close cohabitation with host’s microorganisms. When nematodes infect host, microbiome composition changes, this can ability control parasites. We aimed find out if small roundworms produce substances that antimicrobial properties respond microbial environment, immune regulatory reactions altered in humans lacking gut microbes. There is no doubt different living intestines alter balance of bacteria. Nonetheless, our knowledge about parasite’s influence remains restricted. The last two decades study revealed type iron utilized activation unique virulence factors. However, some roundworm proteins like P43, makes up portion worm’s excretory-secretory product, an unknown role. This review explores how bacterial network contributes adaptability opportunistic pathogen, allowing it successfully host environments.

Язык: Английский

Процитировано

0
TGF-β pathways in aging and immunity: lessons from Caenorhabditis elegans DOI Creative Commons
Katerina K. Yamamoto, Cathy Savage‐Dunn

Frontiers in Genetics, Год журнала: 2023, Номер 14

Опубликована: Сен. 5, 2023

The Transforming Growth Factor-β (TGF-β) superfamily of signaling molecules plays critical roles in development, differentiation, homeostasis, and disease. Due to the conservation these ligands their pathways, genetic studies invertebrate systems including nematode Caenorhabditis elegans have been instrumental identifying mechanisms. C. is also a premier organism for research longevity healthy aging. Here we summarize current knowledge on TGF-β aging immunity.

Язык: Английский

Процитировано

9
Genome-wide analysis of Smad and Schnurri transcription factors in C. elegans demonstrates widespread interaction and a function in collagen secretion DOI Creative Commons
Mehul Vora, Jonathan Dietz,

Zachary Wing

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Авг. 19, 2024

Smads and their transcription factor partners mediate the transcriptional responses of target cells to secreted ligands transforming growth factor-β (TGF-β) family, including those conserved bone morphogenetic protein (BMP) yet only a small number direct genes have been well characterized. In C. elegans, BMP2/4 ortholog DBL-1 regulates multiple biological functions, body size, via canonical receptor-Smad signaling cascade. Here, we identify functional binding sites for SMA-3/Smad its partner SMA-9/Schnurri based on ChIP-seq peaks (identified by modEncode) expression differences nearby identified from RNA-seq analysis corresponding mutants. We found that SMA-3 SMA-9 both overlapping unique genes. At genome-wide scale, acts as activator, whereas targets include activated repressed Mutations in sma-9 partially suppress size phenotype sma-3, suggesting some level antagonism between these factors challenging prevailing model Schnurri function. Functional revealed novel role involved one-carbon metabolism endoplasmic reticulum (ER) secretory pathway, disulfide reductase dpy-11. Our findings indicate previously unappreciated complex genetic genomic regulatory interactions turn regulate secretion extracellular components like collagen into cuticle regulation.

Язык: Английский

Процитировано

1
TGF-β Ligand Cross-Subfamily Interactions in the Response ofCaenorhabditis elegansto Bacterial Pathogens DOI Creative Commons

Emma Jo Ciccarelli,

Zachary Wing,

Moshe Bendelstein

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Май 8, 2023

The Transforming Growth Factor beta (TGF-β) family consists of numerous secreted peptide growth factors that play significant roles in cell function, tissue patterning, and organismal homeostasis, including wound repair immunity. Typically studied as homodimers, these ligands have the potential to diversify their functions through ligand interactions are synergistic, cooperative, additive, and/or antagonistic. In nematode

Язык: Английский

Процитировано

2
Genome-wide analysis of Smad and Schnurri transcription factors inC. elegansdemonstrates widespread interaction and a function in collagen secretion DOI Creative Commons
Mehul Vora, Jonathan Dietz,

Zachary Wing

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 6, 2024

Smads and their transcription factor partners mediate the transcriptional responses of target cells to secreted ligands Transforming Growth Factor-β (TGF-β) family, including those conserved bone morphogenetic protein (BMP) yet only a small number direct genes have been well characterized. In C. elegans, BMP2/4 ortholog DBL-1 regulates multiple biological functions, body size, via canonical receptor-Smad signaling cascade. Here, we identify functional binding sites for SMA-3/Smad its partner SMA-9/Schnurri based on ChIP-seq peaks (identified by modEncode) expression differences nearby identified from RNA-seq analysis corresponding mutants. We found that SMA-3 SMA-9 both overlapping unique genes. At genome-wide scale, acts as activator, whereas targets include activated repressed Mutations in sma-9 partially suppress size phenotype sma-3, suggesting some level antagonism between these factors challenging prevailing model Schnurri function. Functional revealed novel role involved one-carbon metabolism endoplasmic reticulum (ER) secretory pathway, disulfide reductase dpy-11. Our findings indicate previously unappreciated complex genetic genomic regulatory interactions turn regulate secretion extracellular components like collagen into cuticle regulation.

Язык: Английский

Процитировано

0