title: Diverse patterns of genomic targeting by transcriptional regulators in Drosophila melanogaster.
abstract: Annotation of regulatory elements and identification of the transcription-related factors (TRFs) targeting these elements are key steps in understanding how cells interpret their genetic blueprint and their environment during development, and how that process goes awry in the case of disease. One goal of the modENCODE (model organism ENCyclopedia of DNA Elements) Project is to survey a diverse sampling of TRFs, both DNA-binding and non-DNA-binding factors, to provide a framework for the subsequent study of the mechanisms by which transcriptional regulators target the genome. Here we provide an updated map of the Drosophila melanogaster regulatory genome based on the location of 84 TRFs at various stages of development. This regulatory map reveals a variety of genomic targeting patterns, including factors with strong preferences toward proximal promoter binding, factors that target intergenic and intronic DNA, and factors with distinct chromatin state preferences. The data also highlight the stringency of the Polycomb regulatory network, and show association of the Trithorax-like (Trl) protein with hotspots of DNA binding throughout development. Furthermore, the data identify more than 5800 instances in which TRFs target DNA regions with demonstrated enhancer activity. Regions of high TRF co-occupancy are more likely to be associated with open enhancers used across cell types, while lower TRF occupancy regions are associated with complex enhancers that are also regulated at the epigenetic level. Together these data serve as a resource for the research community in the continued effort to dissect transcriptional regulatory mechanisms directing Drosophila development.
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: Matthew
authors.initials: M
authors.lastname: Slattery
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: Lijia
authors.initials: L
authors.lastname: Ma
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Spokony
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: Robert K
authors.initials: RK
authors.lastname: Arthur
authors.affiliation: Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA;
authors.forename: Pouya
authors.initials: P
authors.lastname: Kheradpour
authors.affiliation: Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA;
authors.forename: Anshul
authors.initials: A
authors.lastname: Kundaje
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA; Université de Montpellier II and INRA, UMR1333 DGIMI, F-34095 Montpellier, France;
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nègre
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: Alex
authors.initials: A
authors.lastname: Crofts
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: Ryan
authors.initials: R
authors.lastname: Ptashkin
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zieba
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: Alexander
authors.initials: A
authors.lastname: Ostapenko
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: Sarah
authors.initials: S
authors.lastname: Suchy
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: Alec
authors.initials: A
authors.lastname: Victorsen
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: Nader
authors.initials: N
authors.lastname: Jameel
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: A Jason
authors.initials: AJ
authors.lastname: Grundstad
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: Wenxuan
authors.initials: W
authors.lastname: Gao
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Moran
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: E Jay
authors.initials: EJ
authors.lastname: Rehm
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: Robert L
authors.initials: RL
authors.lastname: Grossman
authors.affiliation: Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA; Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.affiliation: Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: Kevin P
authors.initials: KP
authors.lastname: White
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D049750:Genome, Insect; D023281:Genomics / Q000379:methods; D059372:Nucleotide Motifs; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D014157:Transcription Factors