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...

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Autores principales:	Ryan Z Friedman, David M Granas, Connie A Myers, Joseph C Corbo, Barak A Cohen, Michael A White
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	enhancers silencers information theory massively parallel reporter assays Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/84316855e8ba44709990ec78c1d8425e
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spelling	oai:doaj.org-article:84316855e8ba44709990ec78c1d8425e2021-11-15T06:44:39ZInformation content differentiates enhancers from silencers in mouse photoreceptors10.7554/eLife.674032050-084Xe67403https://doaj.org/article/84316855e8ba44709990ec78c1d8425e2021-09-01T00:00:00Zhttps://elifesciences.org/articles/67403https://doaj.org/toc/2050-084XEnhancers 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.Ryan Z FriedmanDavid M GranasConnie A MyersJoseph C CorboBarak A CohenMichael A WhiteeLife Sciences Publications Ltdarticleenhancerssilencersinformation theorymassively parallel reporter assaysMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	enhancers silencers information theory massively parallel reporter assays Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	enhancers silencers information theory massively parallel reporter assays Medicine R Science Q Biology (General) QH301-705.5 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
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.
format	article
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
title	Information content differentiates enhancers from silencers in mouse photoreceptors
title_short	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_sort	information content differentiates enhancers from silencers in mouse photoreceptors
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/84316855e8ba44709990ec78c1d8425e
work_keys_str_mv	AT ryanzfriedman informationcontentdifferentiatesenhancersfromsilencersinmousephotoreceptors AT davidmgranas informationcontentdifferentiatesenhancersfromsilencersinmousephotoreceptors AT connieamyers informationcontentdifferentiatesenhancersfromsilencersinmousephotoreceptors AT josephccorbo informationcontentdifferentiatesenhancersfromsilencersinmousephotoreceptors AT barakacohen informationcontentdifferentiatesenhancersfromsilencersinmousephotoreceptors AT michaelawhite informationcontentdifferentiatesenhancersfromsilencersinmousephotoreceptors
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Information content differentiates enhancers from silencers in mouse photoreceptors

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