RESUMO
Understanding the in vivo dynamics of protein localization and their physical interactions is important for many problems in biology. To enable systematic protein function interrogation in a multicellular context, we built a genome-scale transgenic platform for in vivo expression of fluorescent- and affinity-tagged proteins in Caenorhabditis elegans under endogenous cis regulatory control. The platform combines computer-assisted transgene design, massively parallel DNA engineering, and next-generation sequencing to generate a resource of 14,637 genomic DNA transgenes, which covers 73% of the proteome. The multipurpose tag used allows any protein of interest to be localized in vivo or affinity purified using standard tag-based assays. We illustrate the utility of the resource by systematic chromatin immunopurification and automated 4D imaging, which produced detailed DNA binding and cell/tissue distribution maps for key transcription factor proteins.
Assuntos
Animais Geneticamente Modificados , Proteínas de Caenorhabditis elegans/análise , Caenorhabditis elegans/genética , Engenharia Genética/métodos , Genoma Helmíntico , Fatores de Transcrição/análise , Animais , Caenorhabditis elegans/química , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Fatores de Transcrição/genéticaRESUMO
In this Review, the year of publication of reference 54 should be 2005, not 2015. In Box 2, "1982: GenBank ( https://www.ncbi.nlm.nih.gov/genbank/statistics/ )" should read "1982: Genbank/ENA/DDBJ" and "2007: NCBI Short Read Archive" should read "2007: NCBI and ENA Short Read Archives"; this is because the launches of these American, European and Japanese databases were coordinated. These errors have not been corrected.
RESUMO
Recently developed single-cell technologies allow researchers to characterize cell states at ever greater resolution and scale. Caenorhabditis elegans is a particularly tractable system for studying development, and recent single-cell RNA-seq studies characterized the gene expression patterns for nearly every cell type in the embryo and at the second larval stage (L2). Gene expression patterns give insight about gene function and into the biochemical state of different cell types; recent advances in other single-cell genomics technologies can now also characterize the regulatory context of the genome that gives rise to these gene expression levels at a single-cell resolution. To explore the regulatory DNA of individual cell types in C. elegans, we collected single-cell chromatin accessibility data using the sci-ATAC-seq assay in L2 larvae to match the available single-cell RNA-seq data set. By using a novel implementation of the latent Dirichlet allocation algorithm, we identify 37 clusters of cells that correspond to different cell types in the worm, providing new maps of putative cell type-specific gene regulatory sites, with promise for better understanding of cellular differentiation and gene regulation.
Assuntos
Caenorhabditis elegans , Cromatina , Animais , Caenorhabditis elegans/genética , Cromatina/genética , Sequenciamento de Cromatina por Imunoprecipitação , DNA/genética , Regulação da Expressão GênicaRESUMO
This review commemorates the 40th anniversary of DNA sequencing, a period in which we have already witnessed multiple technological revolutions and a growth in scale from a few kilobases to the first human genome, and now to millions of human and a myriad of other genomes. DNA sequencing has been extensively and creatively repurposed, including as a 'counter' for a vast range of molecular phenomena. We predict that in the long view of history, the impact of DNA sequencing will be on a par with that of the microscope.
Assuntos
Análise de Sequência de DNA , Animais , Genômica , História do Século XX , História do Século XXI , Humanos , Metagenoma/genética , Microscopia , Análise de Sequência de DNA/história , Análise de Sequência de DNA/métodos , Análise de Sequência de DNA/tendênciasRESUMO
Chromatin immunoprecipitation (IP) followed by sequencing (ChIP-seq) is the gold standard to detect transcription-factor (TF) binding sites in the genome. Its success depends on appropriate controls removing systematic biases. The predominantly used controls, i.e. DNA input, correct for uneven sonication, but not for nonspecific interactions of the IP antibody. Another type of controls, 'mock' IP, corrects for both of the issues, but is not widely used because it is considered susceptible to technical noise. The tradeoff between the two control types has not been investigated systematically. Therefore, we generated comparable DNA input and mock IP experiments. Because mock IPs contain only nonspecific interactions, the sites predicted from them using DNA input indicate the spurious-site abundance. This abundance is highly correlated with the 'genomic activity' (e.g. chromatin openness). In particular, compared to cell lines, complex samples such as whole organisms have more spurious sites-probably because they contain multiple cell types, resulting in more expressed genes and more open chromatin. Consequently, DNA input and mock IP controls performed similarly for cell lines, whereas for complex samples, mock IP substantially reduced the number of spurious sites. However, DNA input is still informative; thus, we developed a simple framework integrating both controls, improving binding site detection.
Assuntos
Sequenciamento de Cromatina por Imunoprecipitação/métodos , Fatores de Transcrição/metabolismo , Anticorpos , Sítios de Ligação , Linhagem Celular , DNA , HumanosRESUMO
We have used RNA-seq in Caenorhabditis elegans to produce transcription profiles for seven specific embryonic cell populations from gastrulation to the onset of terminal differentiation. The expression data for these seven cell populations, covering major cell lineages and tissues in the worm, reveal the complex and dynamic changes in gene expression, both spatially and temporally. Also, within genes, start sites and exon usage can be highly differential, producing transcripts that are specific to developmental periods or cell lineages. We have also found evidence of novel exons and introns, as well as differential usage of SL1 and SL2 splice leaders. By combining this data set with the modERN ChIP-seq resource, we are able to support and predict gene regulatory relationships. The detailed information on differences and similarities between gene expression in cell lineages and tissues should be of great value to the community and provides a framework for the investigation of expression in individual cells.
Assuntos
Processamento Alternativo , Caenorhabditis elegans/genética , Desenvolvimento Embrionário/genética , Transcriptoma , Animais , Caenorhabditis elegans/embriologia , Biologia Computacional/métodos , Éxons , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Íntrons , Anotação de Sequência Molecular , Especificidade de Órgãos , Edição de RNA , Sítios de Splice de RNARESUMO
Gene duplication and deletion are pivotal processes shaping the structural and functional repertoire of genomes, with implications for disease, adaptation, and evolution. We employed a mutation accumulation (MA) framework partnered with high-throughput genomics to assess the molecular and transcriptional characteristics of newly arisen gene copy-number variants (CNVs) in Caenorhabditis elegans populations subjected to varying intensity of selection. Here, we report a direct spontaneous genome-wide rate of gene duplication of 2.9 × 10-5/gene per generation in C. elegans, the highest for any species to date. The rate of gene deletion is sixfold lower (5 × 10-6/gene per generation). Deletions of highly expressed genes are particularly deleterious, given their paucity in even the N = 1 lines with minimal efficacy of selection. The increase in average transcript abundance of new duplicates arising under minimal selection is significantly greater than twofold compared with single copies of the same gene, suggesting that genes in segmental duplications are frequently overactive at inception. The average increase in transcriptional activity of gene duplicates is greater in the N = 1 MA lines than in MA lines with larger population bottlenecks. There is an inverse relationship between the ancestral transcription levels of new gene duplicates and population size, with duplicate copies of highly expressed genes less likely to accumulate in larger populations. Our results demonstrate a fitness cost of increased transcription following duplication, which results in purifying selection against new gene duplicates. However, on average, duplications also provide a significant increase in gene expression that can facilitate adaptation to novel environmental challenges.
Assuntos
Adaptação Fisiológica/genética , Caenorhabditis elegans , Deleção de Genes , Dosagem de Genes , Duplicação Gênica , Transcrição Gênica , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Estudo de Associação Genômica AmplaRESUMO
John Sulston changed the way we do science, not once, but three times - initially with the complete cell lineage of the nematode Caenorhabditis elegans, next with completion of the genome sequences of the worm and human genomes and finally with his strong and active advocacy for open data sharing. His contributions were widely recognized and in 2002 he received the Nobel Prize in Physiology and Medicine.
Assuntos
Biologia do Desenvolvimento/história , Neurociências/história , Animais , Caenorhabditis elegans/citologia , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Linhagem da Célula , Clonagem Molecular/métodos , Mapeamento de Sequências Contíguas/história , Criopreservação , Biblioteca Gênica , Genoma , História do Século XX , História do Século XXI , Projeto Genoma Humano/história , Humanos , Larva , Sistema Nervoso/citologia , Sistema Nervoso/embriologia , Sistema Nervoso/crescimento & desenvolvimento , Neurônios/citologia , Análise de Sequência de DNA/história , Transmissão SinápticaRESUMO
Discovering the structure and dynamics of transcriptional regulatory events in the genome with cellular and temporal resolution is crucial to understanding the regulatory underpinnings of development and disease. We determined the genomic distribution of binding sites for 92 transcription factors and regulatory proteins across multiple stages of Caenorhabditis elegans development by performing 241 ChIP-seq (chromatin immunoprecipitation followed by sequencing) experiments. Integration of regulatory binding and cellular-resolution expression data produced a spatiotemporally resolved metazoan transcription factor binding map. Using this map, we explore developmental regulatory circuits that encode combinatorial logic at the levels of co-binding and co-expression of transcription factors, characterizing the genomic coverage and clustering of regulatory binding, the binding preferences of, and biological processes regulated by, transcription factors, the global transcription factor co-associations and genomic subdomains that suggest shared patterns of regulation, and identifying key transcription factors and transcription factor co-associations for fate specification of individual lineages and cell types.
Assuntos
Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Genoma Helmíntico/genética , Análise Espaço-Temporal , Fatores de Transcrição/metabolismo , Animais , Sítios de Ligação , Caenorhabditis elegans/citologia , Caenorhabditis elegans/embriologia , Proteínas de Caenorhabditis elegans/metabolismo , Linhagem da Célula , Imunoprecipitação da Cromatina , Genômica , Larva/citologia , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Ligação ProteicaRESUMO
Despite the large evolutionary distances between metazoan species, they can show remarkable commonalities in their biology, and this has helped to establish fly and worm as model organisms for human biology. Although studies of individual elements and factors have explored similarities in gene regulation, a large-scale comparative analysis of basic principles of transcriptional regulatory features is lacking. Here we map the genome-wide binding locations of 165 human, 93 worm and 52 fly transcription regulatory factors, generating a total of 1,019 data sets from diverse cell types, developmental stages, or conditions in the three species, of which 498 (48.9%) are presented here for the first time. We find that structural properties of regulatory networks are remarkably conserved and that orthologous regulatory factor families recognize similar binding motifs in vivo and show some similar co-associations. Our results suggest that gene-regulatory properties previously observed for individual factors are general principles of metazoan regulation that are remarkably well-preserved despite extensive functional divergence of individual network connections. The comparative maps of regulatory circuitry provided here will drive an improved understanding of the regulatory underpinnings of model organism biology and how these relate to human biology, development and disease.
Assuntos
Caenorhabditis elegans/genética , Drosophila melanogaster/genética , Evolução Molecular , Regulação da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Fatores de Transcrição/metabolismo , Animais , Sítios de Ligação , Caenorhabditis elegans/crescimento & desenvolvimento , Imunoprecipitação da Cromatina , Sequência Conservada/genética , Drosophila melanogaster/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento/genética , Genoma/genética , Humanos , Anotação de Sequência Molecular , Motivos de Nucleotídeos/genética , Especificidade de Órgãos/genética , Fatores de Transcrição/genéticaRESUMO
We generated detailed RNA-seq data for the nematode Caenorhabditis elegans with high temporal resolution in the embryo as well as representative samples from post-embryonic stages across the life cycle. The data reveal that early and late embryogenesis is accompanied by large numbers of genes changing expression, whereas fewer genes are changing in mid-embryogenesis. This lull in genes changing expression correlates with a period during which histone mRNAs produce almost 40% of the RNA-seq reads. We find evidence for many more splice junctions than are annotated in WormBase, with many of these suggesting alternative splice forms, often with differential usage over the life cycle. We annotated internal promoter usage in operons using SL1 and SL2 data. We also uncovered correlated transcriptional programs that span >80 kb. These data provide detailed annotation of the C. elegans transcriptome.
Assuntos
Caenorhabditis elegans/genética , Regulação da Expressão Gênica no Desenvolvimento , Transcriptoma , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Anotação de Sequência MolecularRESUMO
Mitochondrial genomes of metazoans, given their elevated rates of evolution, have served as pivotal markers for phylogeographic studies and recent phylogenetic events. In order to determine the dynamics of spontaneous mitochondrial mutations in small populations in the absence and presence of selection, we evolved mutation accumulation (MA) lines of Caenorhabditis elegans in parallel over 409 consecutive generations at three varying population sizes of N = 1, 10, and 100 hermaphrodites. The N =1 populations should have a minimal influence of natural selection to provide the spontaneous mutation rate and the expected rate of neutral evolution, whereas larger population sizes should experience increasing intensity of selection. New mutations were identified by Illumina paired-end sequencing of 86 mtDNA genomes across 35 experimental lines and compared with published genomes of natural isolates. The spontaneous mitochondrial mutation rate was estimated at 1.05 × 10-7/site/generation. A strong G/CâA/T mutational bias was observed in both the MA lines and the natural isolates. This suggests that the low G + C content at synonymous sites is the product of mutation bias rather than selection as previously proposed. The mitochondrial effective population size per worm generation was estimated to be 62. Although it was previously concluded that heteroplasmy was rare in C. elegans, the vast majority of mutations in this study were heteroplasmic despite an experimental regime exceeding 400 generations. The frequencies of frameshift and nonsynonymous mutations were negatively correlated with population size, which suggests their deleterious effects on fitness and a potent role for selection in their eradication.
Assuntos
Genoma Mitocondrial/genética , Seleção Genética/genética , Animais , Evolução Biológica , Caenorhabditis elegans/genética , DNA Mitocondrial/genética , Evolução Molecular , Mitocôndrias/genética , Mutação , Acúmulo de Mutações , Taxa de Mutação , Filogenia , Filogeografia , Densidade Demográfica , Análise de Sequência de DNA/métodosRESUMO
We have created a library of 2007 mutagenized Caenorhabditis elegans strains, each sequenced to a target depth of 15-fold coverage, to provide the research community with mutant alleles for each of the worm's more than 20,000 genes. The library contains over 800,000 unique single nucleotide variants (SNVs) with an average of eight nonsynonymous changes per gene and more than 16,000 insertion/deletion (indel) and copy number changes, providing an unprecedented genetic resource for this multicellular organism. To supplement this collection, we also sequenced 40 wild isolates, identifying more than 630,000 unique SNVs and 220,000 indels. Comparison of the two sets demonstrates that the mutant collection has a much richer array of both nonsense and missense mutations than the wild isolate set. We also find a wide range of rDNA and telomere repeat copy number in both sets. Scanning the mutant collection for molecular phenotypes reveals a nonsense suppressor as well as strains with higher levels of indels that harbor mutations in DNA repair genes and strains with abundant males associated with him mutations. All the strains are available through the Caenorhabditis Genetics Center and all the sequence changes have been deposited in WormBase and are available through an interactive website.
Assuntos
Caenorhabditis elegans/genética , Genes de Helmintos , Mutação , Alelos , Animais , Caenorhabditis elegans/classificação , Códon sem Sentido , Variações do Número de Cópias de DNA , DNA Ribossômico , Bases de Dados de Ácidos Nucleicos , Genes Essenciais , Genes Supressores , Variação Genética , Genoma Helmíntico , Genoma Mitocondrial , Heterozigoto , Mutação INDEL , Masculino , Mutação de Sentido Incorreto , Fenótipo , Polimorfismo de Nucleotídeo Único , Sequências de Repetição em TandemRESUMO
How cells adopt different expression patterns is a fundamental question of developmental biology. We quantitatively measured reporter expression of 127 genes, primarily transcription factors, in every cell and with high temporal resolution in C. elegans embryos. Embryonic cells are highly distinct in their gene expression; expression of the 127 genes studied here can distinguish nearly all pairs of cells, even between cells of the same tissue type. We observed recurrent lineage-regulated expression patterns for many genes in diverse contexts. These patterns are regulated in part by the TCF-LEF transcription factor POP-1. Other genes' reporters exhibited patterns correlated with tissue, position, and left-right asymmetry. Sequential patterns both within tissues and series of sublineages suggest regulatory pathways. Expression patterns often differ between embryonic and larval stages for the same genes, emphasizing the importance of profiling expression in different stages. This work greatly expands the number of genes in each of these categories and provides the first large-scale, digitally based, cellular resolution compendium of gene expression dynamics in live animals. The resulting data sets will be a useful resource for future research.
Assuntos
Caenorhabditis elegans/embriologia , Caenorhabditis elegans/genética , Regulação da Expressão Gênica no Desenvolvimento , Genes Reporter , Animais , Padronização Corporal , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Divisão Celular , Linhagem da Célula , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Desenvolvimento Embrionário , Perfilação da Expressão Gênica , Proteínas de Grupo de Alta Mobilidade/genética , Proteínas de Grupo de Alta Mobilidade/metabolismo , Especificidade de Órgãos , Regiões Promotoras Genéticas , Elementos Reguladores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Trans-splicing of one of two short leader RNAs, SL1 or SL2, occurs at the 5' ends of pre-mRNAs of many C. elegans genes. We have exploited RNA-sequencing data from the modENCODE project to analyze the transcriptome of C. elegans for patterns of trans-splicing. Transcripts of â¼70% of genes are trans-spliced, similar to earlier estimates based on analysis of far fewer genes. The mRNAs of most trans-spliced genes are spliced to either SL1 or SL2, but most genes are not trans-spliced to both, indicating that SL1 and SL2 trans-splicing use different underlying mechanisms. SL2 trans-splicing occurs in order to separate the products of genes in operons genome wide. Shorter intercistronic distance is associated with greater use of SL2. Finally, increased use of SL1 trans-splicing to downstream operon genes can indicate the presence of an extra promoter in the intercistronic region, creating what has been termed a "hybrid" operon. Within hybrid operons the presence of the two promoters results in the use of the two SL classes: Transcription that originates at the promoter upstream of another gene creates a polycistronic pre-mRNA that receives SL2, whereas transcription that originates at the internal promoter creates transcripts that receive SL1. Overall, our data demonstrate that >17% of all C. elegans genes are in operons.
Assuntos
Caenorhabditis elegans/genética , Trans-Splicing/genética , Animais , DNA Intergênico/genética , Deleção de Genes , Masculino , Anotação de Sequência Molecular , Óperon/genética , Regiões Promotoras Genéticas , Precursores de RNA/genética , Precursores de RNA/metabolismo , Sítios de Splice de RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Líder para Processamento/genética , RNA Líder para Processamento/metabolismoRESUMO
We present an integrative machine learning method, incRNA, for whole-genome identification of noncoding RNAs (ncRNAs). It combines a large amount of expression data, RNA secondary-structure stability, and evolutionary conservation at the protein and nucleic-acid level. Using the incRNA model and data from the modENCODE consortium, we are able to separate known C. elegans ncRNAs from coding sequences and other genomic elements with a high level of accuracy (97% AUC on an independent validation set), and find more than 7000 novel ncRNA candidates, among which more than 1000 are located in the intergenic regions of C. elegans genome. Based on the validation set, we estimate that 91% of the approximately 7000 novel ncRNA candidates are true positives. We then analyze 15 novel ncRNA candidates by RT-PCR, detecting the expression for 14. In addition, we characterize the properties of all the novel ncRNA candidates and find that they have distinct expression patterns across developmental stages and tend to use novel RNA structural families. We also find that they are often targeted by specific transcription factors (â¼59% of intergenic novel ncRNA candidates). Overall, our study identifies many new potential ncRNAs in C. elegans and provides a method that can be adapted to other organisms.
Assuntos
Caenorhabditis elegans/genética , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência com Séries de Oligonucleotídeos , RNA não Traduzido/química , RNA não Traduzido/genética , Algoritmos , Animais , Sítios de Ligação/genética , DNA Intergênico/genética , Perfilação da Expressão Gênica , Anotação de Sequência Molecular , Conformação de Ácido Nucleico , RNA Polimerase II/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Regulation of gene expression by sequence-specific transcription factors is central to developmental programs and depends on the binding of transcription factors with target sites in the genome. To date, most such analyses in Caenorhabditis elegans have focused on the interactions between a single transcription factor with one or a few select target genes. As part of the modENCODE Consortium, we have used chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq) to determine the genome-wide binding sites of 22 transcription factors (ALR-1, BLMP-1, CEH-14, CEH-30, EGL-27, EGL-5, ELT-3, EOR-1, GEI-11, HLH-1, LIN-11, LIN-13, LIN-15B, LIN-39, MAB-5, MDL-1, MEP-1, PES-1, PHA-4, PQM-1, SKN-1, and UNC-130) at diverse developmental stages. For each factor we determined candidate gene targets, both coding and non-coding. The typical binding sites of almost all factors are within a few hundred nucleotides of the transcript start site. Most factors target a mixture of coding and non-coding target genes, although one factor preferentially binds to non-coding RNA genes. We built a regulatory network among the 22 factors to determine their functional relationships to each other and found that some factors appear to act preferentially as regulators and others as target genes. Examination of the binding targets of three related HOX factors--LIN-39, MAB-5, and EGL-5--indicates that these factors regulate genes involved in cellular migration, neuronal function, and vulval differentiation, consistent with their known roles in these developmental processes. Ultimately, the comprehensive mapping of transcription factor binding sites will identify features of transcriptional networks that regulate C. elegans developmental processes.
Assuntos
Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Fatores de Transcrição/metabolismo , Animais , Sítios de Ligação/genética , Caenorhabditis elegans/citologia , Análise por Conglomerados , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Modelos Teóricos , Dados de Sequência Molecular , RNA não Traduzido/metabolismo , Fatores de Transcrição/genética , Sítio de Iniciação de TranscriçãoRESUMO
The proper development of multicellular organisms requires precise regulation and coordination of cell fate specification, cell proliferation and differentiation. Abnormal regulation and coordination of these processes could lead to disease, including cancer. We have examined the function of the sole C. elegans SoxC protein, SEM-2, in the M lineage, which produces the postembryonic mesoderm. We found that SEM-2/SoxC is both necessary and sufficient to promote a proliferating blast cell fate, the sex myoblast fate, over a differentiated striated bodywall muscle fate. A number of factors control the specific expression of sem-2 in the sex myoblast precursors and their descendants. This includes direct control of sem-2 expression by a Hox-PBC complex. The crucial nature of the HOX/PBC factors in directly enhancing expression of this proliferative factor in the C. elegans M lineage suggests a possible more general link between Hox-PBC factors and SoxC proteins in regulating cell proliferation.
Assuntos
Proteínas de Caenorhabditis elegans/fisiologia , Diferenciação Celular , Proliferação de Células , Mesoderma/crescimento & desenvolvimento , Fatores de Transcrição SOXC/fisiologia , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Diferenciação Celular/genética , Linhagem da Célula/genética , Embrião não Mamífero , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/fisiologia , Mesoderma/embriologia , Mesoderma/metabolismo , Modelos Biológicos , Elementos Reguladores de Transcrição/fisiologia , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/fisiologiaRESUMO
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.