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SIRT6 Overexpression Counteracts Chromatin Aging [ATAC-Seq_tg]

GSE294103 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 28 samples Submitted 2026/04/12 Platform GPL24247
Summary
Aging is associated with detrimental changes in chromatin structure and gene expression, contributing to inflammation, metabolic decline and tissue dysfunction. SIRT6, a histone deacetylase, plays a key role in maintaining chromatin integrity and promoting longevity. Here, we show that aging leads to increased chromatin accessibility in the murine liver, accompanied by upregulation of inflammation and downregulation of metabolic pathways. Remarkably, SIRT6 overexpression reversed these changes, reducing inflammation and enhancing metabolic function. Notably, ETS family members were enriched in regions with increased accessibility during aging, while liver-enriched transcription factors (LETFs) were enriched in regions with reduced accessibility. ChIP-seq analyses of H3K9ac and H3K56ac binding showed that H3K9ac, but not H3K56ac, is associated with increased accessibility during aging, and that SIRT6 can reverse this effect. Furthermore, AAV-mediated SIRT6 overexpression in aged mice demonstrated that SIRT6 not only slows age-related chromatin changes but can also reverse them, rejuvenating chromatin accessibility to a youthful state.
Published in
SIRT6 overexpression counteracts chromatin aging in the male murine liver
Nagar R, Schwartz Z, Katz A et al. · Nature communications 2026 · PMID 42135312 · doi:10.1038/s41467-026-73115-y
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Direct links to NCBI, no account and no request form: the whole study as GSE294103_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 28 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1248381 and SRA study SRP577387. Searching any of these in the dataset finder brings you back here.

Study design
8 × atacseq_tg, young_wt vs 8 × atacseq_tg, old_wt vs 6 × atacseq_tg, young_sirt6_tg vs 6 × atacseq_tg, old_sirt6_tg

Supports a between-group comparison across 28 samples.

4 replicated groups read from 28 sample titles; they account for 28 of them. Check it against the sample list below before relying on it.

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