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Binding profiles for 954 Drosophila and C. elegans transcription factors reveal tissue specific regulatory relationships.

ABSTRACT: A catalog of transcription factor (TF) binding sites in the genome is critical for deciphering regulatory relationships. Here we present the culmination of the modERN (model organism Encyclopedia of Regulatory Networks) consortium that systematically assayed TF binding events in vivo in two major model organisms, Drosophila melanogaster (fly) and Caenorhabditis elegans (worm). We describe key features of these datasets, comprising 604 TFs identifying 3.6M sites in the fly and 350 TFs identifying 0.9 M sites in the worm. Applying a machine learning model to these data identifies sets of TFs with a prominent role in promoting target gene expression in specific cell types. TF binding data are available through the ENCODE Data Coordinating Center and at https://epic.gs.washington.edu/modERNresource, which provides access to processed and summary data, as well as widgets to probe cell type-specific TF-target relationships. These data are a rich resource that should fuel investigations into TF function during development.

SUBMITTER: Kudron M

PROVIDER: S-EPMC10827215 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Binding profiles for 954 Drosophila and C. elegans transcription factors reveal tissue specific regulatory relationships.

Kudron Michelle M Gevirtzman Louis L Victorsen Alec A Lear Bridget C BC Gao Jiahao J Xu Jinrui J Samanta Swapna S Frink Emily E Tran-Pearson Adri A Huynh Chau C Vafeados Dionne D Hammonds Ann A Fisher William W Wall Martha M Wesseling Greg G Hernandez Vanessa V Lin Zhichun Z Kasparian Mary M White Kevin K Allada Ravi R Gerstein Mark M Hillier LaDeana L Celniker Susan E SE Reinke Valerie V Waterston Robert H RH

bioRxiv : the preprint server for biology 20240120

A catalog of transcription factor (TF) binding sites in the genome is critical for deciphering regulatory relationships. Here we present the culmination of the modERN (model organism Encyclopedia of Regulatory Networks) consortium that systematically assayed TF binding events in vivo in two major model organisms, Drosophila melanogaster (fly) and Caenorhabditis elegans (worm). We describe key features of these datasets, comprising 604 TFs identifying 3.6M sites in the fly and 350 T ...[more]

PMID: 38293065

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Project description:BackgroundTranscription regulatory networks are composed of interactions between transcription factors and their target genes. Whereas unicellular networks have been studied extensively, metazoan transcription regulatory networks remain largely unexplored. Caenorhabditis elegans provides a powerful model to study such metazoan networks because its genome is completely sequenced and many functional genomic tools are available. While C. elegans gene predictions have undergone continuous refinement, this is not true for the annotation of functional transcription factors. The comprehensive identification of transcription factors is essential for the systematic mapping of transcription regulatory networks because it enables the creation of physical transcription factor resources that can be used in assays to map interactions between transcription factors and their target genes.ResultsBy computational searches and extensive manual curation, we have identified a compendium of 934 transcription factor genes (referred to as wTF2.0). We find that manual curation drastically reduces the number of both false positive and false negative transcription factor predictions. We discuss how transcription factor splice variants and dimer formation may affect the total number of functional transcription factors. In contrast to mouse transcription factor genes, we find that C. elegans transcription factor genes do not undergo significantly more splicing than other genes. This difference may contribute to differences in organism complexity. We identify candidate redundant worm transcription factor genes and orthologous worm and human transcription factor pairs. Finally, we discuss how wTF2.0 can be used together with physical transcription factor clone resources to facilitate the systematic mapping of C. elegans transcription regulatory networks.ConclusionwTF2.0 provides a starting point to decipher the transcription regulatory networks that control metazoan development and function.

Dataset Information

Binding profiles for 954 Drosophila and C. elegans transcription factors reveal tissue specific regulatory relationships.

Publications

Binding profiles for 954 Drosophila and <i>C. elegans</i> transcription factors reveal tissue specific regulatory relationships.

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