A competitive precision CRISPR method to identify the fitness effects of transcription factor binding sites

Here we describe a competitive genome editing method that measures the effect of mutations on molecular functions, based on precision CRISPR editing using template libraries with either the original or altered sequence, and a sequence tag, enabling direct comparison between original and mutated cell...

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Autores principales: Pihlajamaa, Päivi, Kauko, Otto, Sahu, Biswajyoti, Kivioja, Teemu, Taipale, Jussi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2022
Materias:
Brief Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931575/
https://www.ncbi.nlm.nih.gov/pubmed/36163549
http://dx.doi.org/10.1038/s41587-022-01444-6
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author Pihlajamaa, Päivi
Kauko, Otto
Sahu, Biswajyoti
Kivioja, Teemu
Taipale, Jussi
author_facet Pihlajamaa, Päivi
Kauko, Otto
Sahu, Biswajyoti
Kivioja, Teemu
Taipale, Jussi
author_sort Pihlajamaa, Päivi
collection PubMed
description Here we describe a competitive genome editing method that measures the effect of mutations on molecular functions, based on precision CRISPR editing using template libraries with either the original or altered sequence, and a sequence tag, enabling direct comparison between original and mutated cells. Using the example of the MYC oncogene, we identify important transcriptional targets and show that E-box mutations at MYC target gene promoters reduce cellular fitness.
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spelling pubmed-99315752023-02-17 A competitive precision CRISPR method to identify the fitness effects of transcription factor binding sites Pihlajamaa, Päivi Kauko, Otto Sahu, Biswajyoti Kivioja, Teemu Taipale, Jussi Nat Biotechnol Brief Communication Here we describe a competitive genome editing method that measures the effect of mutations on molecular functions, based on precision CRISPR editing using template libraries with either the original or altered sequence, and a sequence tag, enabling direct comparison between original and mutated cells. Using the example of the MYC oncogene, we identify important transcriptional targets and show that E-box mutations at MYC target gene promoters reduce cellular fitness. Nature Publishing Group US 2022-09-26 2023 /pmc/articles/PMC9931575/ /pubmed/36163549 http://dx.doi.org/10.1038/s41587-022-01444-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Brief Communication
Pihlajamaa, Päivi
Kauko, Otto
Sahu, Biswajyoti
Kivioja, Teemu
Taipale, Jussi
A competitive precision CRISPR method to identify the fitness effects of transcription factor binding sites
title A competitive precision CRISPR method to identify the fitness effects of transcription factor binding sites
title_full A competitive precision CRISPR method to identify the fitness effects of transcription factor binding sites
title_fullStr A competitive precision CRISPR method to identify the fitness effects of transcription factor binding sites
title_full_unstemmed A competitive precision CRISPR method to identify the fitness effects of transcription factor binding sites
title_short A competitive precision CRISPR method to identify the fitness effects of transcription factor binding sites
title_sort competitive precision crispr method to identify the fitness effects of transcription factor binding sites
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931575/
https://www.ncbi.nlm.nih.gov/pubmed/36163549
http://dx.doi.org/10.1038/s41587-022-01444-6
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