Information content differentiates enhancers from silencers in mouse photoreceptors
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-09-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/67403 |
| _version_ | 1828382713301696512 |
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| author | Ryan Z Friedman David M Granas Connie A Myers Joseph C Corbo Barak A Cohen Michael A White |
| author_facet | Ryan Z Friedman David M Granas Connie A Myers Joseph C Corbo Barak A Cohen Michael A White |
| author_sort | Ryan Z Friedman |
| collection | DOAJ |
| description | 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 cone-rod homeobox (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. |
| first_indexed | 2024-12-10T04:37:37Z |
| format | Article |
| id | doaj.art-84316855e8ba44709990ec78c1d8425e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:37:37Z |
| publishDate | 2021-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-84316855e8ba44709990ec78c1d8425e2022-12-22T02:01:58ZengeLife Sciences Publications LtdeLife2050-084X2021-09-011010.7554/eLife.67403Information content differentiates enhancers from silencers in mouse photoreceptorsRyan Z Friedman0https://orcid.org/0000-0001-9013-8676David M Granas1Connie A Myers2Joseph C Corbo3https://orcid.org/0000-0002-9323-7140Barak A Cohen4https://orcid.org/0000-0002-3350-2715Michael A White5https://orcid.org/0000-0001-8511-6026Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, United States; Department of Genetics, Washington University School of Medicine, St. Louis, United StatesEdison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, United States; Department of Genetics, Washington University School of Medicine, St. Louis, United StatesDepartment of Pathology and Immunology, Washington University School of Medicine, St Louis, United StatesDepartment of Pathology and Immunology, Washington University School of Medicine, St Louis, United StatesEdison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, United States; Department of Genetics, Washington University School of Medicine, St. Louis, United StatesEdison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, United States; Department of Genetics, Washington University School of Medicine, St. Louis, United StatesEnhancers 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 cone-rod homeobox (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.https://elifesciences.org/articles/67403enhancerssilencersinformation theorymassively parallel reporter assays |
| spellingShingle | Ryan Z Friedman David M Granas Connie A Myers Joseph C Corbo Barak A Cohen Michael A White Information content differentiates enhancers from silencers in mouse photoreceptors eLife enhancers silencers information theory massively parallel reporter assays |
| title | Information content differentiates enhancers from silencers in mouse photoreceptors |
| title_full | Information content differentiates enhancers from silencers in mouse photoreceptors |
| title_fullStr | Information content differentiates enhancers from silencers in mouse photoreceptors |
| title_full_unstemmed | Information content differentiates enhancers from silencers in mouse photoreceptors |
| title_short | Information content differentiates enhancers from silencers in mouse photoreceptors |
| title_sort | information content differentiates enhancers from silencers in mouse photoreceptors |
| topic | enhancers silencers information theory massively parallel reporter assays |
| url | https://elifesciences.org/articles/67403 |
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