Editing the epigenome: technologies for programmable transcription and epigenetic modulation
Open accessAbstract
Gene regulation is a complex and tightly controlled process that defines cell identity, health and disease, and response to pharmacologic and environmental signals. Recently developed DNA-targeting platforms, including zinc finger proteins, transcription activator-like effectors (TALEs) and the clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 system, have enabled the recruitment of transcriptional modulators and epigenome-modifying factors to any genomic site, leading to new insights into the function of epigenetic marks in gene expression. Additionally, custom transcriptional and epigenetic regulation is facilitating refined control over cell function and decision making. The unique properties of the CRISPR-Cas9 system have created new opportunities for high-throughput genetic screens and multiplexing targets to manipulate complex gene expression patterns. This Review summarizes recent technological developments in this area and their application to biomedical challenges. We also discuss remaining limitations and necessary future directions for this field.
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dCas9-KRAB system reversibly suppresses gene expression through heterochromatin formation and significantly reduced expression of a series of endogenous genes.
“dCas9-KRAB system, recruiting a diverse array of histone modifiers that reversibly suppresses gene expression through the formation of heterochromatin, significantly reduced the expression of a series of endogenous genes in the genome [125, 128].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [128]
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References 174 · Cited by 451
- Authors
- Thakore, P. I., Black, J. B., Hilton, I. B., & Gersbach, C. A.
- Affiliations
- Duke University (US)
- Corresponding author
- Gersbach, Charles A
- Venue
- Nature Methods
- Published
- 2016-01-28
- Volume
- 13
- Issue
- 2
- Pages
- 127-137
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- PMC
- PMC4922638
- OpenAlex
- W2273050936
- Cited by
- 451
- References
- 174
- Citations by year
- 2026: 32 · 2025: 29 · 2024: 39 · 2023: 22 · 2022: 40 · 2021: 44 · 2020: 40 · 2019: 41 · 2018: 68 · 2017: 63 · 2016: 33
- FWCI
- 6.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Methods (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation
- American Heart Association
- National Institutes of Health (1dp2od008586-01)
- National Institute on Drug Abuse (R01DA036865)
- National Human Genome Research Institute (U01HG007900)
- National Institute of General Medical Sciences (T32GM008555)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21AR065956, P30AR066527)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- epigenome editing, CRISPR/Cas9, transcription activator-like effectors, zinc finger proteins, epigenetic modulation, gene expression regulation, transcriptional regulation, epigenetic modifications, high-throughput genetic screens
- MeSH terms
- Animals, Gene Expression Regulation, Genetic Engineering, Transcription, Genetic, Epigenesis, Genetic, Epigenomics, CRISPR-Cas Systems
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