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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.
Pubmed ID: 39887187
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Software tool for automated microscope acquisition, device control, and image analysis. Used for integrating dissimilar fluorescent microscope hardware and peripherals into a single custom workstation, while providing all the tools needed to perform analysis of acquired images. Offers user friendly application modules for analysis such as cell signaling, cell counting, and protein expression.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsA software package that integrates ChIP-seq of transcription factors or chromatin regulators with differential gene expression data to infer direct target genes. BETA has three functions: (1) to predict whether the factor has activating or repressive function; (2) to infer the factor''''s target genes; and (3) to identify the motif of the factor and its collaborators which might modulate the factor''''s activating or repressive function. BETA requires ~2GB RAM and 1h for the whole procedure. BETA may run on the web server at Cistrome or may be downloaded.
View all literature mentionsEncyclopedia of DNA elements consisting of list of functional elements in human genome, including elements that act at protein and RNA levels, and regulatory elements that control cells and circumstances in which gene is active. Enables scientific and medical communities to interpret role of human genome in biology and disease. Provides identification of common cell types to facilitate integrative analysis and new experimental technologies based on high-throughput sequencing. Genome Browser containing ENCODE and Epigenomics Roadmap data. Data are available for entire human genome.
View all literature mentionsBioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.
View all literature mentionsSoftware application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.
View all literature mentionsCaenorhabditis elegans with name nhr-114(gk849) V. from WB.
View all literature mentionsCaenorhabditis elegans with name T24B8.5(ok3236) II. from WB.
View all literature mentionsCentral data repository for nematode biology including complete genomic sequence, gene predictions and orthology assignments from range of related nematodes.Data concerning genetics, genomics and biology of C. elegans and related nematodes. Derived from initial ACeDB database of C. elegans genetic and sequence information, WormBase includes genomic, anatomical and functional information of C. elegans, other Caenorhabditis species and other nematodes. Maintains public FTP site where researchers can find many commonly requested files and datasets, WormBase software and prepackaged databases.
View all literature mentionsCaenorhabditis elegans with name sma-2(e502) III. from WB.
View all literature mentionsCaenorhabditis elegans with name acs-22(gk373989) X. from WB.
View all literature mentionsCaenorhabditis elegans with name lbp-8(gk5151[loxP + myo-3p::GFP::unc-54 3' UTR + rps-27p::neoR::unc-54 3' UTR + loxP]) V. from WB.
View all literature mentionsCaenorhabditis elegans with name fat-7(wa36) V. from WB.
View all literature mentionsCaenorhabditis elegans with name Caenorhabditis elegans wild isolate. from WB.
View all literature mentionsCaenorhabditis elegans with name clec-60(tm2319) II. from WB.
View all literature mentionsCaenorhabditis elegans with name fat-6(tm331) IV. from WB.
View all literature mentionsCaenorhabditis elegans with name sma-9(ok1628) X. from WB.
View all literature mentionsCaenorhabditis elegans with name ZK1251.1&ins-7(ok1573) IV. from WB.
View all literature mentionsCaenorhabditis elegans with name rrf-3(pk1426) II. from WB.
View all literature mentions