Ethylene plays pleiotropic roles in plant growth, plant development, and stress responses. Although the effects of ethylene on plants are well documented, little is known about molecular-level events that result in transcriptional activation and repression during the ethylene response. Here, we show that ethylene specifically elevates acetylation of histone H3K14 and H3K23 in etiolated seedlings. The up-regulation of these two histone marks positively correlates with ethylene-regulated transcription activation, and the elevation requires EIN2. EIN2 C terminus (EIN2-C) associates with histone partially through an interaction with a SANT domain protein named EIN2 nuclear associated protein 1 (ENAP1). Specifically, in the presence of ethylene, ENAP1-binding regions are more accessible upon the interaction with EIN2, and more EIN3 proteins bind to the loci where ENAP1 is enriched for a quick response. On the other hand, we found that two histone deacetylases, SRT1 and SRT2, interact with ENAP1, which associates with EIN2 in the nucleus. Genetic and transcriptome analyses revealed that SRT1 and SRT2 are required for negative regulation of certain ethylene-responsive genes. The acetylation of HISTONE3 at K9 (H3K9Ac) is specifically regulated by SRT1 and SRT2 in ethylene-repressed genes. SRT2 and ENAP1 both bind to promoter regions of genes negatively regulated by ethylene, reducing H3K9Ac levels and resulting in transcriptional repression.