دورية أكاديمية
Temporal and Spatial Epigenome Editing Allows Precise Gene Regulation in Mammalian Cells
| العنوان: | Temporal and Spatial Epigenome Editing Allows Precise Gene Regulation in Mammalian Cells |
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| المؤلفون: | Mammeadov, R., Kuscu, C., Czikora, A., Unlu, H., Tufan, T., Fischer, N.L., Arslan, Åževki |
| بيانات النشر: | Academic Press |
| سنة النشر: | 2019 |
| المجموعة: | Pamukkale University Repository / Pamukkale Üniversitesi Açık Erişim Arşivi |
| مصطلحات موضوعية: | CRISPR, AID (auxin-inducible degron), enhancer-like elements, non-regulatory regions, p300, auxin, histone H3, messenger RNA, MyoD1 protein, octamer transcription factor 4, guide RNA, CRISPR associated protein, E1A associated p300 protein, EP300 protein, human, Article, chromatin, clustered regularly interspaced short palindromic repeat, controlled study, enhancer region, epigenetics, gene control, gene editing, gene expression regulation, HEK293T cell line, human cell, K-562 cell line, mammal cell, priority journal, promoter region |
| الوصف: | Cell-type specific gene expression programs are tightly linked to epigenetic modifications on DNA and histone proteins. Here, we used a novel CRISPR-based epigenome editing approach to control gene expression spatially and temporally. We show that targeting dCas9–p300 complex to distal non-regulatory genomic regions reprograms the chromatin state of these regions into enhancer-like elements. Notably, through controlling the spatial distance of these induced enhancers (i-Enhancer) to the promoter, the gene expression amplitude can be tightly regulated. To better control the temporal persistence of induced gene expression, we integrated the auxin-inducible degron technology with CRISPR tools. This approach allows rapid depletion of the dCas9-fused epigenome modifier complex from the target site and enables temporal control over gene expression regulation. Using this tool, we investigated the temporal persistence of a locally edited epigenetic mark and its functional consequences. The tools and approaches presented here will allow novel insights into the mechanism of epigenetic memory and gene regulation from distal regulatory sites. © 2018 |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0022-2836 |
| العلاقة: | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı; https://hdl.handle.net/11499/30290Test; https://doi.org/10.1016/j.jmb.2018.08.001Test; 431; 111; 121; 2-s2.0-85051629890; WOS:000456222200009 |
| DOI: | 10.1016/j.jmb.2018.08.001 |
| الإتاحة: | https://doi.org/10.1016/j.jmb.2018.08.001Test https://hdl.handle.net/11499/30290Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.43EC55D7 |
| قاعدة البيانات: | BASE |
| تدمد: | 00222836 |
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| DOI: | 10.1016/j.jmb.2018.08.001 |