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Gene expression + ATAC profiling of trisomic hippocampal neurons upon SAHA treatment [ATAC-seq]

GSE328495 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 16 samples Submitted 2026/08/07 Platform GPL17021
Summary
Down syndrome (DS) is associated with widespread molecular alterations, including aberrant gene expression, which not only affects chromosome 21 genes but perturbs the whole transcriptome. The genome-wide nature of this alteration suggests that it might be epigenetically mediated, which may also offer therapeutic opportunities given the reversibility of epigenetic modifications. Here, we show that decreased global acetylation level in the hippocampus of the trisomic mouse model Ts65Dn is associated with decreased chromatin accessibility at gene promoters in hippocampal neurons. Strikingly, pharmacological restoration of histone acetylation using the clinically approved histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) normalized transcriptomic, epigenetic and cortico-hippocampal memory deficits in trisomic mice. This rescue was mediated by an unexpected heterochromatization of the supernumerary chromosome. Altogether, our results identify an unanticipated epigenetic mechanism linking histone acetylation dynamics to chromosomal dosage homeostasis.
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Direct links to NCBI, no account and no request form: the whole study as GSE328495_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 16 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1455549 and SRA study SRP693168. Searching any of these in the dataset finder brings you back here.

Study design
16 conditions, each sampled once — no replicated groups

Read from 16 sample titles: 16 distinct titles with little repetition. Check it against the sample list below before relying on it.

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