GEO series

SIRT6-dependent functional switch via K494 modifications of RE-1 Silencing Transcription factor [REST_experiment_2]

GSE261903 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 30 samples Submitted 2025/03/19 Platform GPL9052

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 30 samples

What it is: ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism: Homo sapiens (human)
Samples: 30 samples: 10 conditions, mostly in triplicateGroups 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)

RE-1 Silencing Transcription factor (REST) is a key repressor of neural genesREST functions as a key factor for cell differentiation, repressing neural genes in non-neural somatic tissues. REST is upregulated under stress signals, aging, and neurodegenerative diseases, but loses its function in Alzheimer's Disease. However, why it becomes inactive remains unclear.

Read the full summary ↓

Here we show that the NAD-dependent deacetylase SIRT6 regulates REST expression, location, and activity. In SIRT6 absence, REST is overexpressed, but mis localized and inactive. SIRT6 deficiency abrogates REST and EZH2 interaction, perturbs its location to heterochromatin Lamin B ring, and leads to REST target gene overexpression. SIRT6 reintroduction or REST methyl-mimic K494M expression rescues this phenotype, while an acetyl-mimic mutant loses its function even in WT cells. Our studies define a novel regulatory switch, where the function of a critical repressor is regulated by post-translational modifications on K494 depending on SIRT6 existence, in turn modulating neuronal gene expression.

This dataset

Open GSE261903 in finder → Find more human ChIP / ATAC / CUT&Tag datasets →

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.

Series matrix ↓

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 GSE261903_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

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.

Raw reads on ENA ↗

What the files usually look like: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1089558 and SRA study SRP496407. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

10 conditions, mostly in triplicate

CC,ChIP,K494A, ×3 CC,ChIP,K494M, ×3 CC,ChIP,K494Q, ×3 CC,ChIP,WT, ×3 CC,ChIP,Flag-CMV, ×3 CC,Input,K494A, ×3 CC,Input,K494M, ×3 CC,Input,K494Q, ×3 +2 more

Supports a between-group comparison across 30 samples.

How we read this: 10 replicated groups read from 30 sample titles; they account for 30 of them. 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

GSM8153868 CC,ChIP,K494A,rep1 CC,ChIP,K494A,
GSM8153869 CC,ChIP,K494A,rep2 CC,ChIP,K494A,
GSM8153870 CC,ChIP,K494A,rep3 CC,ChIP,K494A,
GSM8153871 CC,ChIP,K494M,rep1 CC,ChIP,K494M,
GSM8153872 CC,ChIP,K494M,rep2 CC,ChIP,K494M,
GSM8153873 CC,ChIP,K494M,rep3 CC,ChIP,K494M,
GSM8153874 CC,ChIP,K494Q,rep1 CC,ChIP,K494Q,
GSM8153875 CC,ChIP,K494Q,rep2 CC,ChIP,K494Q,
GSM8153876 CC,ChIP,K494Q,rep3 CC,ChIP,K494Q,
GSM8153877 CC,ChIP,WT,rep1 CC,ChIP,WT,
GSM8153878 CC,ChIP,WT,rep2 CC,ChIP,WT,
GSM8153879 CC,ChIP,WT,rep3 CC,ChIP,WT,
GSM8153880 CC,ChIP,Flag-CMV,rep1 CC,ChIP,Flag-CMV,
GSM8153881 CC,ChIP,Flag-CMV,rep2 CC,ChIP,Flag-CMV,
GSM8153882 CC,ChIP,Flag-CMV,rep3 CC,ChIP,Flag-CMV,
GSM8153883 CC,Input,K494A,rep1 CC,Input,K494A,
GSM8153884 CC,Input,K494A,rep2 CC,Input,K494A,
GSM8153885 CC,Input,K494A,rep3 CC,Input,K494A,
GSM8153886 CC,Input,K494M,rep1 CC,Input,K494M,
GSM8153887 CC,Input,K494M,rep2 CC,Input,K494M,
GSM8153888 CC,Input,K494M,rep3 CC,Input,K494M,
GSM8153889 CC,Input,K494Q,rep1 CC,Input,K494Q,
GSM8153890 CC,Input,K494Q,rep2 CC,Input,K494Q,
GSM8153891 CC,Input,K494Q,rep3 CC,Input,K494Q,
GSM8153892 CC,Input,WT,rep1 CC,Input,WT,
GSM8153893 CC,Input,WT,rep2 CC,Input,WT,
GSM8153894 CC,Input,WT,rep3 CC,Input,WT,
GSM8153895 CC,Input,Flag-CMV,rep1 CC,Input,Flag-CMV,
GSM8153896 CC,Input,Flag-CMV,rep2 CC,Input,Flag-CMV,
GSM8153897 CC,Input,Flag-CMV,rep3 CC,Input,Flag-CMV,

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