Publication

Inhibition of histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing

Liu, B., Chen, S., Chen, D., Cao, F., Zwinderman, M., Kiemel, D., Aïssi, M., Dekker, F. J., Haisma, H. J. & La Rose, A., 4-Dec-2019, In : Nucleic Acids Research. 16 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Liu, B., Chen, S., Chen, D., Cao, F., Zwinderman, M., Kiemel, D., ... La Rose, A. (2019). Inhibition of histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing. Nucleic Acids Research. https://doi.org/10.1093/nar/gkz1136

Author

Liu, Bin ; Chen, Siwei ; Chen, Deng ; Cao, Fangyuan ; Zwinderman, Martijn ; Kiemel, Dominik ; Aïssi, Manon ; Dekker, Frank J. ; Haisma, Hidde J. ; La Rose, Anouk. / Inhibition of histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing. In: Nucleic Acids Research. 2019.

Harvard

Liu, B, Chen, S, Chen, D, Cao, F, Zwinderman, M, Kiemel, D, Aïssi, M, Dekker, FJ, Haisma, HJ & La Rose, A 2019, 'Inhibition of histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing', Nucleic Acids Research. https://doi.org/10.1093/nar/gkz1136

Standard

Inhibition of histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing. / Liu, Bin; Chen, Siwei; Chen, Deng; Cao, Fangyuan; Zwinderman, Martijn; Kiemel, Dominik; Aïssi, Manon; Dekker, Frank J.; Haisma, Hidde J.; La Rose, Anouk.

In: Nucleic Acids Research, 04.12.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Liu B, Chen S, Chen D, Cao F, Zwinderman M, Kiemel D et al. Inhibition of histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing. Nucleic Acids Research. 2019 Dec 4. https://doi.org/10.1093/nar/gkz1136


BibTeX

@article{986eb1c832664aa98ddd153a096e56c9,
title = "Inhibition of histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing",
abstract = "Despite the rapid development of CRISPR/Cas9-mediated gene editing technology, the gene editing potential of CRISPR/Cas9 is hampered by low efficiency, especially for clinical applications. One of the major challenges is that chromatin compaction inevitably limits the Cas9 protein access to the target DNA. However, chromatin compaction is precisely regulated by histone acetylation and deacetylation. To overcome these challenges, we have comprehensively assessed the impacts of histone modifiers such as HDAC (1-9) inhibitors and HAT (p300/CBP, Tip60 and MOZ) inhibitors, on CRISPR/Cas9 mediated gene editing efficiency. Our findings demonstrate that attenuation of HDAC1, HDAC2 activity, but not other HDACs, enhances CRISPR/Cas9-mediated gene knockout frequencies by NHEJ as well as gene knock-in by HDR. Conversely, inhibition of HDAC3 decreases gene editing frequencies. Furthermore, our study showed that attenuation of HDAC1, HDAC2 activity leads to an open chromatin state, facilitates Cas9 access and binding to the targeted DNA and increases the gene editing frequencies. This approach can be applied to other nucleases, such as ZFN and TALEN.",
author = "Bin Liu and Siwei Chen and Deng Chen and Fangyuan Cao and Martijn Zwinderman and Dominik Kiemel and Manon A{\"i}ssi and Dekker, {Frank J.} and Haisma, {Hidde J.} and {La Rose}, Anouk",
note = "{\circledC} The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.",
year = "2019",
month = "12",
day = "4",
doi = "10.1093/nar/gkz1136",
language = "English",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",

}

RIS

TY - JOUR

T1 - Inhibition of histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing

AU - Liu, Bin

AU - Chen, Siwei

AU - Chen, Deng

AU - Cao, Fangyuan

AU - Zwinderman, Martijn

AU - Kiemel, Dominik

AU - Aïssi, Manon

AU - Dekker, Frank J.

AU - Haisma, Hidde J.

AU - La Rose, Anouk

N1 - © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.

PY - 2019/12/4

Y1 - 2019/12/4

N2 - Despite the rapid development of CRISPR/Cas9-mediated gene editing technology, the gene editing potential of CRISPR/Cas9 is hampered by low efficiency, especially for clinical applications. One of the major challenges is that chromatin compaction inevitably limits the Cas9 protein access to the target DNA. However, chromatin compaction is precisely regulated by histone acetylation and deacetylation. To overcome these challenges, we have comprehensively assessed the impacts of histone modifiers such as HDAC (1-9) inhibitors and HAT (p300/CBP, Tip60 and MOZ) inhibitors, on CRISPR/Cas9 mediated gene editing efficiency. Our findings demonstrate that attenuation of HDAC1, HDAC2 activity, but not other HDACs, enhances CRISPR/Cas9-mediated gene knockout frequencies by NHEJ as well as gene knock-in by HDR. Conversely, inhibition of HDAC3 decreases gene editing frequencies. Furthermore, our study showed that attenuation of HDAC1, HDAC2 activity leads to an open chromatin state, facilitates Cas9 access and binding to the targeted DNA and increases the gene editing frequencies. This approach can be applied to other nucleases, such as ZFN and TALEN.

AB - Despite the rapid development of CRISPR/Cas9-mediated gene editing technology, the gene editing potential of CRISPR/Cas9 is hampered by low efficiency, especially for clinical applications. One of the major challenges is that chromatin compaction inevitably limits the Cas9 protein access to the target DNA. However, chromatin compaction is precisely regulated by histone acetylation and deacetylation. To overcome these challenges, we have comprehensively assessed the impacts of histone modifiers such as HDAC (1-9) inhibitors and HAT (p300/CBP, Tip60 and MOZ) inhibitors, on CRISPR/Cas9 mediated gene editing efficiency. Our findings demonstrate that attenuation of HDAC1, HDAC2 activity, but not other HDACs, enhances CRISPR/Cas9-mediated gene knockout frequencies by NHEJ as well as gene knock-in by HDR. Conversely, inhibition of HDAC3 decreases gene editing frequencies. Furthermore, our study showed that attenuation of HDAC1, HDAC2 activity leads to an open chromatin state, facilitates Cas9 access and binding to the targeted DNA and increases the gene editing frequencies. This approach can be applied to other nucleases, such as ZFN and TALEN.

U2 - 10.1093/nar/gkz1136

DO - 10.1093/nar/gkz1136

M3 - Article

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

ER -

ID: 86222041