Information content differentiates enhancers from silencers in mouse photoreceptors
- Washington University School of Medicine, United States
Abstract
Enhancers and silencers often depend on the same transcription factors (TFs) and are conflated in genomic assays of TF binding or chromatin state. To identify sequence features that distinguish enhancers and silencers, we assayed massively parallel reporter libraries of genomic sequences targeted by the photoreceptor TF CRX in mouse retinas. Both enhancers and silencers contain more TF motifs than inactive sequences, but relative to silencers, enhancers contain motifs from a more diverse collection of TFs. We developed a measure of information content that describes the number and diversity of motifs in a sequence and found that, while both enhancers and silencers depend on CRX motifs, enhancers have higher information content. The ability of information content to distinguish enhancers and silencers targeted by the same TF illustrates how motif context determines the activity of cis-regulatory sequences.
Data availability
The pJK01 and pJK03 plasmids have been deposited with AddGene (IDs 173489, 173490). Raw sequencing data and barcode counts have been uploaded to the NCBI GEO database under accession GSE165812. All processed activity data, predicted occupancy, and information content values are available in the supplementary material. All code for data processing, analysis, and visualization is available on Github at https://github.com/barakcohenlab/CRX-Information-Content.
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Information Content Differentiates Enhancers From Silencers in Mouse PhotoreceptorsNCBI Gene Expression Omnibus, GSE165812.
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Deciphering the cis-regulatory architecture of mammalian photoreceptorsNCBI Gene Expression Omnibus, GSE20012.
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ATAC-seq and RNA-seq of adult mouse rods and conesNCBI Gene Expression Omnibus, GSE83312.
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Transcriptional Regulation of Rod Photoreceptor Homeostasis Revealed by In Vivo NRL Targetome AnalysisNEI Data Share, Hong PLoS-Genet-2012.
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MEF2D drives photoreceptor development through a genome-wide competition for tissue-specific enhancersNCBI Gene Expression Omnibus, GSE61392.
Article and author information
Author details
Funding
National Institutes of Health (F31HG011431)
- Ryan Z Friedman
National Institutes of Health (R01GM121755)
- Michael A White
National Institutes of Health (R01EY027784)
- Barak A Cohen
National Institutes of Health (EY025196)
- Joseph C Corbo
National Institutes of Health (EY03075)
- Joseph C Corbo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Naama Barkai, Weizmann Institute of Science, Israel
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to protocol # A-3381-01 approved by the Institutional Animal Care and Use Committee of Washington University in St. Louis. Euthanasia of mice was performed according to the recommendations of the American Veterinary Medical Association Guidelines on Euthanasia. Appropriate measures are taken to minimize pain and discomfort to the animals during experimental procedures.
Version history
- Preprint posted: February 7, 2021 (view preprint)
- Received: February 9, 2021
- Accepted: September 3, 2021
- Accepted Manuscript published: September 6, 2021 (version 1)
- Version of Record published: October 5, 2021 (version 2)
Copyright
© 2021, Friedman et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Information content differentiates enhancers from silencers in mouse photoreceptors
eLife 10:e67403.
https://doi.org/10.7554/eLife.67403
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