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MORC3 represses a tandem repeat enhancer to regulate interferon

GSE301805 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 22 samples Submitted 2026/03/09 Platform GPL34281Platform GPL34284
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 22 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
22 samples: 10 conditions, mostly in duplicateGroups 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.
Paper
MORC3 represses a tandem repeat enhancer to regulate interferonThe EMBO journal · 2026
Summary (written by the submitters)
The antiviral protein MORC3 is frequently inhibited by viruses. To counteract viral antagonism, MORC3 represses a noncanonical pathway of type-I-interferon (IFN) such that viral inhibition of MORC3 triggers (>10,000-fold) IFN induction. How MORC3 represses this pathway, and why IFN induction upon MORC3 loss is so potent without canonical IRF3/7 transcription factors, is unknown.
Read the full summary ↓
Here, we show that MORC3 restricts chromatin accessibility at tandem repeat elements harboring up to 61 homotypic transcription factor motifs. One such element becomes a potent enhancer of IFNB1 upon MORC3 loss. Its motif cluster contains 45 PU.1 binding sites and is necessary and sufficient for MORC3-mediated repression and enhancer activity upon MORC3 loss. PU.1 recruits MORC3 to repress this enhancer by recruiting DAXX and enabling H3.3 incorporation. Upon MORC3 loss, PU.1 drives IRF3/7-independent IFN induction. Other restricted tandem repeats contain homotypic motif clusters of SPI, AP-1, and SP/KLF transcription factors. Our findings uncover a TF motif cluster–driven repression mechanism by MORC3 at tandem repeats, enabling specific repression of an IFNB1 enhancer such that viral antagonism of MORC3 induces interferon.
Published in
MORC3 represses a tandem repeat enhancer to regulate interferon
Krumwiede L, Hollaus D, Valeri E et al. · The EMBO journal 2026 · PMID 42249047 · doi:10.1038/s44318-026-00799-9
This dataset
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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 GSE301805_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 PRJNA1287590 and SRA study SRP598894. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42249047) ↗
Study design
10 conditions, mostly in duplicate
MORC3 ChIP-Seq input, replicate 1, ×2 MORC3 ChIP-Seq input, replicate 2, ×2 MORC3 ChIP-Seq, replicate 1, ×2 MORC3 ChIP-Seq, replicate 2, ×2 Input for PU.1 ChIP-Seq in MORC3.AID.V5 cells, ×2 PU.1 ChIP-Seq in MORC3.AID.V5 cells treated w… ×2 PU.1 ChIP-Seq in MORC3.AID.V5 cells treated w… ×2 ChIP-Seq Input for V5(MORC3) ChIP in MORC3.AI… ×2 +4 more

Supports a between-group comparison across 20 samples.

How we read this: 10 replicated groups read from 22 sample titles; they account for 20 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
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