التفاصيل البيبلوغرافية
| العنوان: |
Temporal and Spatial Epigenome Editing Allows Precise Gene Regulation in Mammalian Cells |
| المؤلفون: |
Natasha Lopes Fischer, Rashad Mammadov, Stefan Bekiranov, Hayrunnisa Unlu, Turan Tufan, Cem Kuscu, Mazhar Adli, Sevki Arslan, Masato T. Kanemaki, Agnes Czikora |
| المصدر: |
Journal of molecular biology. 431(1) |
| سنة النشر: |
2018 |
| مصطلحات موضوعية: |
CRISPR-Associated Proteins, EP300 protein, human, K-562 cell line, CRISPR Cas system, 0302 clinical medicine, histone H3, Structural Biology, CRISPR, RNA, Guide, genetics, Clustered Regularly Interspaced Short Palindromic Repeats, Promoter Regions, Genetic, non-regulatory regions, Regulation of gene expression, Gene Editing, 0303 health sciences, biology, messenger RNA, gene control, gene expression regulation, Chromatin, Histone, priority journal, HEK293 cell line, enhancer region, RNA, Guide, Kinetoplastida, octamer transcription factor 4, E1A associated p300 protein, HEK293T cell line, p300, Computational biology, Article, Cell Line, CRISPR-Associated Proteins/*genetics, CRISPR-Cas Systems/*genetics, Clustered Regularly Interspaced Short Palindromic Repeats/*genetics, E1A-Associated p300 Protein/*genetics, Gene Editing/*methods, Gene Expression Regulation, HEK293 Cells, Humans, Promoter Regions, Genetic/genetics, RNA, Guide/genetics, 03 medical and health sciences, CRISPR associated protein, promoter region, Epigenome editing, MyoD1 protein, controlled study, Epigenetics, AID (auxin-inducible degron), human, procedures, Enhancer, Molecular Biology, 030304 developmental biology, enhancer-like elements, epigenetics, human cell, Epigenome, guide RNA, biology.protein, chromatin, CRISPR-Cas Systems, auxin, mammal cell, E1A-Associated p300 Protein, 030217 neurology & neurosurgery, clustered regularly interspaced short palindromic repeat |
| 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 |
| وصف الملف: |
application/pdf |
| تدمد: |
1089-8638 |
| الوصول الحر: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3162e4123e128e44c4adb6a91a18b072Test
https://pubmed.ncbi.nlm.nih.gov/30098338Test |
| حقوق: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....3162e4123e128e44c4adb6a91a18b072 |
| قاعدة البيانات: |
OpenAIRE |
