Influence of catalytic and non-catalytic functions of class I HDACs on the cellular transcriptome

We generated a cellular class I HDAC toolbox allowing to discriminate between catalytic and non-catalytic roles of class I HDACs. Our study reveals a comprehensive, functional analysis of class I HDACs. HAP1 cell lines lacking individual HDACs or expressing catalytically inactive, transgenic isoforms were used for gene expression analysis. We demonstrate that HDAC1 and HDAC2 have crucial, partially overlapping functions in the regulation of gene expression. Disrupting HDAC3 caused major changes in the transcriptome, indicating that this enzyme has unique regulatory roles. Furthermore, cells expressing inactive HDAC1, HDAC2 and HDAC8 better mimicked HDAC inhibitor treated cells compared to their respective knockouts. 3 biological replica were analyzed of each cell line or treatment condition, including: 1) control cell line (untreated), 2) cells with knockout of individual class I HDACs, 3) cells expressing inactive transgenic HDAC from the AAVS1 locus in the control background, 4) cells expressing either active or inactive transgenic HDAC from the AAVS1 locus in the corresponding knockout background, 4) cells treated with MS-275, 5) cells treated with JQ12