GEO series

SIRT6 Overexpression Counteracts Chromatin Aging [ChIP-Seq]

GSE294085 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 74 samples Submitted 2026/04/12 Platform GPL34290

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

This dataset

Open GSE294085 in finder → Find more mouse ChIP / ATAC / CUT&Tag datasets →

Download

Direct links to NCBI, no account and no request form: the whole study as GSE294085_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 74 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1248043 and SRA study SRP577283. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42135312) ↗

Study design

8 conditions, mostly with about 6 replicates each

H3K9ac_H3K56ac_Input_old_wt ×6 H3K9ac_H3K56ac_Input_old_sirt6_tg ×6 H3K9ac_old_wt ×6 H3K9ac_old_sirt6_tg ×6 H3K9ac_H3K56ac_Input_young_wt ×4 H3K9ac_H3K56ac_Input_young_sirt6_tg ×4 H3K9ac_young_wt ×4 H3K9ac_young_sirt6_tg ×4

Supports a between-group comparison across 40 samples.

8 replicated groups read from the first 40 of 74 sample titles; they account for 40 of them. Check it against the sample list below before relying on it.

Similar datasets

Search all mouse ChIP / ATAC / CUT&Tag datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.