GSE43439
Genomic topography of HDACi-induced hyperacetylation of hippocampal chromatin [ChIP-Seq]
Histone deacetylase inhibitors (HDACis) have been shown to potentiate hippocampal-dependent memory and synaptic plasticity and to ameliorate cognitive deficits and degeneration in animal models for different neuropsychiatric conditions. However, the impact of these drugs on hippocampal histone acetylation and gene expression profiles at the genomic level, and the molecular mechanisms that underlie their specificity and beneficial effects in neural tissue, remains obscure. Here, we mapped four relevant histone marks (H3K4me3, AcH3K9,14, AcH4K12 and pan-AcH2B) in hippocampal chromatin and investigated at the whole-genome level the impact of HDAC inhibition on acetylation profiles and basal and activity-driven gene expression. HDAC inhibition caused a dramatic histone hyperacetylation that was largely restricted to active loci pre-marked with H3K4me3 and AcH3K9,14. In addition, the comparison of Chromatin immunoprecipitation sequencing and gene expression profiles indicated that Trichostatin A-induced histone hyperacetylation, like histone hypoacetylation induced by histone acetyltransferase deficiency, had a modest impact on hippocampal gene expression and did not affect the transient transcriptional response to novelty exposure. However, HDAC inhibition caused the rapid induction of a homeostatic gene program related to chromatin deacetylation. These results illuminate both the relationship between hippocampal gene expression and histone acetylation and the mechanism of action of these important neuropsychiatric drugs. Overall design: Examination of 4 different histone modifications in the hippocampus of vehicle (DMSO/Saline) or HDACi TSA (2.4 mg/kg)-treated mice. Samples were obtained 30 min after intraperitoneal administration of either TSA or Vehicle. NOTE: The ChIPseq experiments described here and those presented in the series GSE44854 were performed in paralell. Therefore, some control samples are part of both datasets (GSM1062434, GSM1062437, GSM1062441 and GSM1062442).