REDfly: the transcriptional regulatory element database for Drosophila

Abstract The REDfly database provides a comprehensive curation of experimentally-validated Drosophila transcriptional cis-regulatory elements and includes information on DNA sequence, experimental evidence, patterns of regulated gene expression, and more. Now in its thirteenth year, REDfly has grown to over 23 000 records of tested reporter gene constructs and 2200 tested transcription factor binding sites. Recent developments include the start of curation of predicted cis-regulatory modules in addition to experimentally-verified ones, improved search and filtering, and increased interaction with the authors of curated papers. An expanded data model that will capture information on temporal aspects of gene regulation, regulation in response to environmental and other non-developmental cues, sexually dimorphic gene regulation, and non-endogenous (ectopic) aspects of reporter gene expression is under development and expected to be in place within the coming year. REDfly is freely accessible at http://redfly.ccr.buffalo.edu, and news about database updates and new features can be followed on Twitter at @REDfly_database.

[1]  Michael P. Eichenlaub,et al.  A temporal map of transcription factor activity: mef2 directly regulates target genes at all stages of muscle development. , 2006, Developmental cell.

[2]  Marc S Halfon,et al.  Computational discovery of cis-regulatory modules in Drosophila without prior knowledge of motifs , 2008, Genome Biology.

[3]  Xiaodong Wang,et al.  The folded k-spectrum kernel: A machine learning approach to detecting transcription factor binding sites with gapped nucleotide dependencies , 2017, PloS one.

[4]  S. Raghav,et al.  A yeast one-hybrid and microfluidics-based pipeline to map mammalian gene regulatory networks , 2013, Molecular systems biology.

[5]  Tamer Kahveci,et al.  Accessed Terms of Use , 2022 .

[6]  E. Furlong,et al.  A core transcriptional network for early mesoderm development in Drosophila melanogaster. , 2007, Genes & development.

[7]  M. Halfon,et al.  Identifying transcriptional cis‐regulatory modules in animal genomes , 2015, Wiley interdisciplinary reviews. Developmental biology.

[8]  Łukasz M. Boryń,et al.  Genome-Wide Quantitative Enhancer Activity Maps Identified by STARR-seq , 2013, Science.

[9]  Long Li,et al.  REDfly: a Regulatory Element Database for Drosophila , 2006, Bioinform..

[10]  Wolfgang Huber,et al.  Enhancer loops appear stable during development and are associated with paused polymerase , 2014, Nature.

[11]  Yanhui Hu,et al.  FlyBase at 25: looking to the future , 2016, Nucleic Acids Res..

[12]  David Osumi-Sutherland,et al.  The Drosophila anatomy ontology , 2013, Journal of Biomedical Semantics.

[13]  J. Reinitz,et al.  Natural variation of the expression pattern of the segmentation gene even-skipped in melanogaster. , 2015, Developmental biology.

[14]  E. Furlong,et al.  Uncoupling evolutionary changes in DNA sequence, transcription factor occupancy and enhancer activity , 2017, eLife.

[15]  Olga G. Troyanskaya,et al.  Probabilistic modelling of chromatin code landscape reveals functional diversity of enhancer-like chromatin states , 2016, Nature Communications.

[16]  E. Furlong,et al.  Dual functionality of cis-regulatory elements as developmental enhancers and Polycomb response elements , 2017, Genes & development.

[17]  Charles Blatti,et al.  Quantitative Analysis of the Drosophila Segmentation Regulatory Network Using Pattern Generating Potentials , 2010, PLoS biology.

[18]  Sebastian J. Maerkl,et al.  Does Positive Selection Drive Transcription Factor Binding Site Turnover? A Test with Drosophila Cis-Regulatory Modules , 2011, PLoS genetics.

[19]  J. Bateman,et al.  The Capacity to Act in Trans Varies Among Drosophila Enhancers , 2016, Genetics.

[20]  Christopher D. Brown,et al.  A Comprehensive Map of Insulator Elements for the Drosophila Genome , 2010, PLoS genetics.

[21]  The Gene Ontology Consortium,et al.  Expansion of the Gene Ontology knowledgebase and resources , 2016, Nucleic Acids Res..

[22]  P. Wittkopp,et al.  Structure of the Transcriptional Regulatory Network Correlates with Regulatory Divergence in Drosophila , 2017, Molecular biology and evolution.

[23]  L. Visai,et al.  Allosteric Regulation of Fibronectin/α5β1 Interaction by Fibronectin-Binding MSCRAMMs , 2016, PloS one.

[24]  S. Sinha,et al.  Redeployment of a conserved gene regulatory network during Aedes aegypti development. , 2016, Developmental biology.

[25]  Paul Marjoram,et al.  Translating natural genetic variation to gene expression in a computational model of the Drosophila gap gene regulatory network , 2017, PloS one.

[26]  T. Brody,et al.  cis-Decoder discovers constellations of conserved DNA sequences shared among tissue-specific enhancers , 2007, Genome Biology.

[27]  James B. Brown,et al.  Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions , 2009, Genome Biology.

[28]  Steven M. Gallo,et al.  REDfly v3.0: toward a comprehensive database of transcriptional regulatory elements in Drosophila , 2010, Nucleic Acids Res..

[29]  Venky N. Iyer,et al.  Sepsid even-skipped Enhancers Are Functionally Conserved in Drosophila Despite Lack of Sequence Conservation , 2008, PLoS genetics.

[30]  Casey M. Bergman,et al.  Drosophila DNase I footprint database: a systematic genome annotation of transcription factor binding sites in the fruitfly, Drosophila melanogaster , 2005, Bioinform..

[31]  D. W. Knowles,et al.  Transcription Factors Bind Thousands of Active and Inactive Regions in the Drosophila Blastoderm , 2008, PLoS biology.

[32]  Melanie A. Huntley,et al.  Evolution of genes and genomes on the Drosophila phylogeny , 2007, Nature.

[33]  Zeba Wunderlich,et al.  An Enhancer's Length and Composition Are Shaped by Its Regulatory Task , 2017, Front. Genet..

[34]  Julie M. Sullivan,et al.  FlyMine: an integrated database for Drosophila and Anopheles genomics , 2007, Genome Biology.

[35]  Md. Abul Hassan Samee,et al.  Quantitative Measurement and Thermodynamic Modeling of Fused Enhancers Support a Two-Tiered Mechanism for Interpreting Regulatory DNA. , 2017, Cell reports.

[36]  Pavel Tomancak,et al.  An alignment-free method to identify candidate orthologous enhancers in multiple Drosophila genomes , 2010, Bioinform..

[37]  Diego Miranda-Saavedra,et al.  Motif-blind, genome-wide discovery of cis-regulatory modules in Drosophila and mouse. , 2009, Developmental cell.

[38]  Steven M. Gallo,et al.  REDfly 2.0: an integrated database of cis-regulatory modules and transcription factor binding sites in Drosophila , 2007, Nucleic Acids Res..

[39]  B. Wilczyński,et al.  Taking promoters out of enhancers in sequence based predictions of tissue-specific mammalian enhancers , 2017, BMC Medical Genomics.

[40]  I. Schor,et al.  The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription , 2018, Genes & development.

[41]  E. Furlong,et al.  Combinatorial binding predicts spatio-temporal cis-regulatory activity , 2009, Nature.

[42]  A. Long,et al.  Fine scale structural variants distinguish the genomes of Drosophila melanogaster and D. pseudoobscura , 2006, Genome Biology.

[43]  O. Elemento,et al.  Unmasking Activation of the Zygotic Genome Using Chromosomal Deletions in the Drosophila Embryo , 2007, PLoS Biology.

[44]  Marc S. Halfon,et al.  Evidence for Deep Regulatory Similarities in Early Developmental Programs across Highly Diverged Insects , 2014, Genome biology and evolution.

[45]  The Gene Ontology Consortium Expansion of the Gene Ontology knowledgebase and resources , 2016, Nucleic Acids Res..

[46]  Marc S. Halfon,et al.  Improved accuracy of supervised CRM discovery with interpolated Markov models and cross-species comparison , 2011, Nucleic acids research.

[47]  Julie H. Simpson,et al.  A GAL4-driver line resource for Drosophila neurobiology. , 2012, Cell reports.

[48]  Qiang Yu,et al.  SMCis: An Effective Algorithm for Discovery of Cis-Regulatory Modules , 2016, PloS one.

[49]  Stein Aerts,et al.  Fine-Tuning Enhancer Models to Predict Transcriptional Targets across Multiple Genomes , 2007, PloS one.

[50]  J. Stamatoyannopoulos,et al.  The role of chromatin accessibility in directing the widespread, overlapping patterns of Drosophila transcription factor binding , 2011, Genome Biology.

[51]  Alisha K Holloway,et al.  Accelerated sequence divergence of conserved genomic elements in Drosophila melanogaster. , 2008, Genome research.

[52]  Marc S Halfon,et al.  Large-scale analysis of transcriptional cis-regulatory modules reveals both common features and distinct subclasses , 2007, Genome Biology.

[53]  Ralf Zimmer,et al.  Cross-species Conservation of context-specific networks , 2016, BMC Systems Biology.

[54]  E. Furlong,et al.  Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development , 2012, Nature Genetics.

[55]  Ryan K. Dale,et al.  RNAi-independent role for Argonaute2 in CTCF/CP190 chromatin insulator function. , 2011, Genes & development.

[56]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[57]  I. Zhimulev,et al.  Chromatin Heterogeneity and Distribution of Regulatory Elements in the Late-Replicating Intercalary Heterochromatin Domains of Drosophila melanogaster Chromosomes , 2016, PloS one.

[58]  Mehmet M. Dalkilic,et al.  Gene networks in Drosophila melanogaster: integrating experimental data to predict gene function , 2009, Genome Biology.

[59]  W. J. Kent,et al.  BLAT--the BLAST-like alignment tool. , 2002, Genome research.

[60]  Ehsan S. Tabari,et al.  De novo prediction of cis-regulatory elements and modules through integrative analysis of a large number of ChIP datasets , 2014, BMC Genomics.