Quantitative-enhancer-FACS-seq (QeFS) reveals epistatic interactions among motifs within transcriptional enhancers in developing Drosophila tissue

Understanding the contributions of transcription factor DNA binding sites to transcriptional enhancers is a significant challenge. We developed Quantitative enhancer-FACS-Seq for highly parallel quantification of enhancer activities from a genomically integrated reporter in Drosophila melanogaster e...

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Autores principales: Waters, Colin T., Gisselbrecht, Stephen S., Sytnikova, Yuliya A., Cafarelli, Tiziana M., Hill, David E., Bulyk, Martha L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Method
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686523/
https://www.ncbi.nlm.nih.gov/pubmed/34930411
http://dx.doi.org/10.1186/s13059-021-02574-x
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author Waters, Colin T.
Gisselbrecht, Stephen S.
Sytnikova, Yuliya A.
Cafarelli, Tiziana M.
Hill, David E.
Bulyk, Martha L.
author_facet Waters, Colin T.
Gisselbrecht, Stephen S.
Sytnikova, Yuliya A.
Cafarelli, Tiziana M.
Hill, David E.
Bulyk, Martha L.
author_sort Waters, Colin T.
collection PubMed
description Understanding the contributions of transcription factor DNA binding sites to transcriptional enhancers is a significant challenge. We developed Quantitative enhancer-FACS-Seq for highly parallel quantification of enhancer activities from a genomically integrated reporter in Drosophila melanogaster embryos. We investigate the contributions of the DNA binding motifs of four poorly characterized TFs to the activities of twelve embryonic mesodermal enhancers. We measure quantitative changes in enhancer activity and discover a range of epistatic interactions among the motifs, both synergistic and alleviating. We find that understanding the regulatory consequences of TF binding motifs requires that they be investigated in combination across enhancer contexts. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-021-02574-x.
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spelling pubmed-86865232021-12-20 Quantitative-enhancer-FACS-seq (QeFS) reveals epistatic interactions among motifs within transcriptional enhancers in developing Drosophila tissue Waters, Colin T. Gisselbrecht, Stephen S. Sytnikova, Yuliya A. Cafarelli, Tiziana M. Hill, David E. Bulyk, Martha L. Genome Biol Method Understanding the contributions of transcription factor DNA binding sites to transcriptional enhancers is a significant challenge. We developed Quantitative enhancer-FACS-Seq for highly parallel quantification of enhancer activities from a genomically integrated reporter in Drosophila melanogaster embryos. We investigate the contributions of the DNA binding motifs of four poorly characterized TFs to the activities of twelve embryonic mesodermal enhancers. We measure quantitative changes in enhancer activity and discover a range of epistatic interactions among the motifs, both synergistic and alleviating. We find that understanding the regulatory consequences of TF binding motifs requires that they be investigated in combination across enhancer contexts. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-021-02574-x. BioMed Central 2021-12-20 /pmc/articles/PMC8686523/ /pubmed/34930411 http://dx.doi.org/10.1186/s13059-021-02574-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Method
Waters, Colin T.
Gisselbrecht, Stephen S.
Sytnikova, Yuliya A.
Cafarelli, Tiziana M.
Hill, David E.
Bulyk, Martha L.
Quantitative-enhancer-FACS-seq (QeFS) reveals epistatic interactions among motifs within transcriptional enhancers in developing Drosophila tissue
title Quantitative-enhancer-FACS-seq (QeFS) reveals epistatic interactions among motifs within transcriptional enhancers in developing Drosophila tissue
title_full Quantitative-enhancer-FACS-seq (QeFS) reveals epistatic interactions among motifs within transcriptional enhancers in developing Drosophila tissue
title_fullStr Quantitative-enhancer-FACS-seq (QeFS) reveals epistatic interactions among motifs within transcriptional enhancers in developing Drosophila tissue
title_full_unstemmed Quantitative-enhancer-FACS-seq (QeFS) reveals epistatic interactions among motifs within transcriptional enhancers in developing Drosophila tissue
title_short Quantitative-enhancer-FACS-seq (QeFS) reveals epistatic interactions among motifs within transcriptional enhancers in developing Drosophila tissue
title_sort quantitative-enhancer-facs-seq (qefs) reveals epistatic interactions among motifs within transcriptional enhancers in developing drosophila tissue
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686523/
https://www.ncbi.nlm.nih.gov/pubmed/34930411
http://dx.doi.org/10.1186/s13059-021-02574-x
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