HDAC1/2/3 Are Major Histone Desuccinylase Critical for Promoter Desuccinylation [RNA-seq]
Lysine succinylation is one of the major post-translational modifications occurred on histones and is believed to have significant roles in regulation of chromatin structure and function. Currently, histone desuccinylation is widely believed to be exerted by the members of SIRT family deacetylases. Here, we report that histone desuccinylation is in fact primarily catalyzed by the class I HDAC1/2/3. Inhibition or depletion of HDAC1/2/3 resulted in marked increase of global histone succinylation, whereas ectopic expression of HDAC1/2/3 but not their deacetylase inactive mutants downregulated global histone succinylation. We demonstrated that the class I HDAC1/2/3 complexes have robust histone desuccinylase activity in vitro. Genomic landscape analysis revealed that histone succinylation is highly enriched at gene promoters and inhibition of HDAC activity results in marked elevation of promoter histone succinylation. Furthermore, integrated analysis revealed that the promoter histone succinylation positively correlates with the transcriptional activity. Collectively, we demonstrate that the class I HDAC1/2/3 but not the SIRT family proteins are the major histone desuccinylases particularly important for promoter histone desuccinylation. Our study thus sheds new light on the role of histone succinylation in transcriptional regulation. Overall design: For RNA-seq analysis, an equivalent number (5 × 106) of DMSO/TSA-treated, control, HDAC1/2/3 knockout or SIRT7 knockout HeLa cells were used for total RNA preparation using Trizol reagent and phenol-chloroform-isopropanol extraction. Library preparation and sequencing were performed by Illumina Hiseq 2500 platform with three independent biological replicates.