Summary• Plant resistance to pathogen attack is often associated with a localized programmed cell death called hypersensitive response (HR). How this cell death is controlled remains largely unknown.• Upon treatment with cryptogein, an elicitor of tobacco defence and cell death, we identified NtHD2a and NtHD2b, two redundant isoforms of type-2 nuclear histone deacetylases (HDACs). These HDACs are phosphorylated after a few minutes' treatment, and their rate of mRNAs are rapidly and strongly reduced, leading to a 40-fold decrease after10 h of treatment.• By using HDAC inhibitors, RNAi-and overexpression-based approaches, we showed that HDACs, and especially NtHD2a ⁄ b, act as inhibitors of cryptogeininduced cell death. Moreover, in NtHD2a ⁄ b-silenced plants, infiltration with cryptogein led to HR-like symptoms in distal leaves.• Taken together, these results show for the first time that type-2 HDACs, which are specific to plants, act as negative regulators of elicitor-induced cell death in tobacco (Nicotiana tabacum), suggesting that the HR is controlled by posttranslational modifications including (de)acetylation of nuclear proteins.

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