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SIRT7 regulates NUCKS1 chromatin binding to elicit metabolic and inflammatory gene expression in senescence and liver aging.

GSE295888 Homo sapiens (human) RNA-seq (gene expression) 30 samples Submitted 2025/06/01 Platform GPL21697Platform GPL21626
At a glance

RNA-seq (gene expression) · human · 30 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
30 samples: 30 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
Sirtuins, a class of highly conserved histone/protein deacetylases, are heavily implicated in senescence and aging. The regulation of sirtuin proteins is tightly controlled both transcriptionally, translationally and via localization within the cell. While Sirtuin proteins are associated with aging, how their levels are regulated during aging across cell types and how they elicit tissue-specific age-related cellular changes are unclear.
Read the full summary ↓
Here, we demonstrate that SIRT7 is targeted for degradation during senescence and liver aging. To uncover the significance and regulation of SIRT7 loss, we performed proteomics analysis and found that the E3 Ligase TRIP12 reduces SIRT7 levels during senescence. We identified the HMG box transcription factor NUCKS1 as a new SIRT7 interactor. We found that NUCKS1 is recruited onto chromatin during senescence, mediated by SIRT7 loss and accompanied by increased NUCKS1 acetylation. Depletion of NUCKS1 delayed senescence upon DNA damage leading to reduced inflammatory gene expression. Examination of transcriptional regulation by NUCKS1 during senescence revealed target genes of transcription factors NFKB1, RELA, and CEBP—all previously associated with senescence. Consistently, in Sirt7 KO mouse liver and in naturally aged livers, NUCKS1 was recruited to chromatin, bound at promoters and enhancers of age-related genes, including transcription factor Rela, and these bound sites had increased accessibility during aging. Overall, our results uncover NUCKS1 as a novel interactor of SIRT7, showing that proteosomal loss of SIRT7 during senescence and liver aging promotes chromatin binding of acetylated NUCKS1 to induce metabolic and inflammatory genes.
This dataset
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE295888_RAW.tar (it can run to tens of gigabytes).

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1256737 and SRA study SRP582154. Searching any of these in the dataset finder brings you back here.

Study design
30 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 30 sample titles: 30 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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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.