Diverse patterns of genomic targeting by transcriptional regulators in Drosophila melanogaster
- Matthew Slattery1,5,6,
- Lijia Ma1,6,
- Rebecca F. Spokony1,6,
- Robert K. Arthur1,
- Pouya Kheradpour2,
- Anshul Kundaje2,
- Nicolas Nègre1,3,
- Alex Crofts1,
- Ryan Ptashkin1,
- Jennifer Zieba1,
- Alexander Ostapenko1,
- Sarah Suchy1,
- Alec Victorsen1,
- Nader Jameel1,
- A. Jason Grundstad1,
- Wenxuan Gao1,
- Jennifer R. Moran1,
- E. Jay Rehm1,
- Robert L. Grossman1,
- Manolis Kellis2,4 and
- Kevin P. White1,7
- 1Institute for Genomics & Systems Biology, Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
- 2Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA;
- 3Université de Montpellier II and INRA, UMR1333 DGIMI, F-34095 Montpellier, France;
- 4Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
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↵6 These authors contributed equally to this work.
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.
Footnotes
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↵7 Corresponding author
E-mail kpwhite{at}uchicago.edu
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.168807.113.
Freely available online through the Genome Research Open Access option.
- Received October 26, 2013.
- Accepted February 14, 2014.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0.
