Temporal and Spatial Epigenome Editing Allows Precise Gene Regulation in Mammalian Cells

Cem Kuscu, Rashad Mammeadov, Agnes Czikora, Hayrunnisa Unlu, Turan Tufan, Natasha Lopes Fischer, Sevki Arslan, Stefan Bekiranov, Masato Kanemaki, Mazhar Adli

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)111-121
Number of pages11
JournalJournal of Molecular Biology
Volume431
Issue number1
DOIs
StatePublished - Jan 4 2019

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Clustered Regularly Interspaced Short Palindromic Repeats
Epigenomics
Gene Expression
Genes
Indoleacetic Acids
Gene Expression Regulation
Histones
Chromatin
Technology
DNA
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology

Cite this

Temporal and Spatial Epigenome Editing Allows Precise Gene Regulation in Mammalian Cells. / Kuscu, Cem; Mammeadov, Rashad; Czikora, Agnes; Unlu, Hayrunnisa; Tufan, Turan; Fischer, Natasha Lopes; Arslan, Sevki; Bekiranov, Stefan; Kanemaki, Masato; Adli, Mazhar.

In: Journal of Molecular Biology, Vol. 431, No. 1, 04.01.2019, p. 111-121.

Research output: Contribution to journalArticle

Kuscu, C, Mammeadov, R, Czikora, A, Unlu, H, Tufan, T, Fischer, NL, Arslan, S, Bekiranov, S, Kanemaki, M & Adli, M 2019, 'Temporal and Spatial Epigenome Editing Allows Precise Gene Regulation in Mammalian Cells', Journal of Molecular Biology, vol. 431, no. 1, pp. 111-121. https://doi.org/10.1016/j.jmb.2018.08.001
Kuscu, Cem ; Mammeadov, Rashad ; Czikora, Agnes ; Unlu, Hayrunnisa ; Tufan, Turan ; Fischer, Natasha Lopes ; Arslan, Sevki ; Bekiranov, Stefan ; Kanemaki, Masato ; Adli, Mazhar. / Temporal and Spatial Epigenome Editing Allows Precise Gene Regulation in Mammalian Cells. In: Journal of Molecular Biology. 2019 ; Vol. 431, No. 1. pp. 111-121.
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