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. 2022 Aug 22;18(8):e1010376. doi: 10.1371/journal.pgen.1010376

Fig 1. Study design.

Fig 1

This study compared effects of genetic and pharmacological inactivation of HDAC1/2/3. Genetically modified cell lines expressing catalytically inactivate (CI) transgenic versions of HDAC1/2/3, in addition to cells treated with HDAC inhibitors, were used. The HDAC CI cell lines were investigated as potential novel tool to mimic partial or full HDAC inactivation. This was achieved by expressing transgenic HDAC1, HDAC2 or HDAC3 in the presence (wildtype background) or absence (knockout background) of the respective endogenous HDAC enzyme. We performed a comprehensive comparative approach using the HDAC1/2/3 CI cell lines and cells treated with the HDAC inhibitors JQ12 and MS-275. Based on global acetylome profiling and gene expression analysis, isoform-specific functions of HDAC1/2 and HDAC3 and similarities between genetic and pharmacological inactivation were investigated. A screening approach with anti-cancer drugs further addressed the question, if the HDAC1/2/3 CI model is suitable to study synergistic effects of isoform-specific HDAC inactivation.