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Information Content Differentiates Enhancers From Silencers in Mouse Photoreceptors

View ORCID ProfileRyan Z. Friedman, David M. Granas, Connie A. Myers, View ORCID ProfileJoseph C. Corbo, View ORCID ProfileBarak A. Cohen, View ORCID ProfileMichael A. White
doi: https://doi.org/10.1101/2021.02.05.429997
Ryan Z. Friedman
1Edison Family Center for Genome Sciences and Systems Biology, and Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA
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David M. Granas
1Edison Family Center for Genome Sciences and Systems Biology, and Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA
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Connie A. Myers
2Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
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Joseph C. Corbo
2Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
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Barak A. Cohen
1Edison Family Center for Genome Sciences and Systems Biology, and Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA
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Michael A. White
1Edison Family Center for Genome Sciences and Systems Biology, and Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA
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  • For correspondence: mawhite@wustl.edu
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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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • We have revised the introduction and discussion sections. We have added a new analysis of RNA-seq data in Crx-/- retinas. We extended the methods to reflect the new analysis. We revised Figure 2D.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 30, 2021.
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Information Content Differentiates Enhancers From Silencers in Mouse Photoreceptors
Ryan Z. Friedman, David M. Granas, Connie A. Myers, Joseph C. Corbo, Barak A. Cohen, Michael A. White
bioRxiv 2021.02.05.429997; doi: https://doi.org/10.1101/2021.02.05.429997
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Information Content Differentiates Enhancers From Silencers in Mouse Photoreceptors
Ryan Z. Friedman, David M. Granas, Connie A. Myers, Joseph C. Corbo, Barak A. Cohen, Michael A. White
bioRxiv 2021.02.05.429997; doi: https://doi.org/10.1101/2021.02.05.429997

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