PT  - JOURNAL ARTICLE
AU  - Bin Liu
AU  - Siwei Chen
AU  - Anouk La Rose
AU  - Deng Chen
AU  - Fangyuan Cao
AU  - Dominik Kiemel
AU  - Manon Aïssi
AU  - FJ Dekker
AU  - HJ Haisma
TI  - Inhibition of Histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing
AID  - 10.1101/670554
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 670554
4099  - http://biorxiv.org/content/early/2019/06/13/670554.short
4100  - http://biorxiv.org/content/early/2019/06/13/670554.full
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.