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., 24-Jan-2020, In : Nucleic Acids Research. 48, 2, p. 517-532 16 p.

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)517-532
Number of pages16
JournalNucleic Acids Research
Volume48
Issue number2
Early online date4-Dec-2019
Publication statusPublished - 24-Jan-2020

Download statistics

No data available

ID: 86222041