GEO series
SUMOylation orchestrates a metastable heterochromatin state on a MORC3-responsive element to silence IFNB1 at a distance [ChIP-seq]
GSE292571
Homo sapiens; Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
116 samples
Submitted 2025/07/17
Platform GPL30173Platform GPL21103Platform GPL30172
Summary
Despite the pleiotropic role of SUMOylation, this pathway mainly functions to repress innate immunity in myeloid cells. Inactivating SUMOylation triggers a potent basal type I interferon (IFN1) response, amplified and coupled with an inflammatory response upon stimulation. These findings transposed to pre-clinical models with the demonstration that SUMOylation inhibitors (SUMOi) activate antitumor immunity in an IFN1-dependent manner. Yet, how SUMOylation represses immune signaling remains largely unknown. We identified murine MORC3, a critical transcriptional repressor of the IFNB1 gene, as the top SUMO2/3 substrate in myeloid cells. We show that, in human monocytes, SUMO functions to repress basal IFNB1 in cis through an atypical/repeated MORC3-regulated element (MRE) concentrating/homing multiple PU.1 binding motifs. Inhibiting SUMOylation induces a 3D genome reorganization centered on the MRE, which, in turn, acquires both insulator and PU.1-driven enhancer activities, together with loss of H3.3 and H3K9me3 repressive marks and increased PU-1 binding. Paradoxically, MORC3, that binds PU.1, is massively recruited, yet unable to repress the MRE. Finally, we show that both MORC3 ATPase cycle and SUMOylation are critical for full MORC3 repressive activity. Our study identifies an unconventional mechanism in which SUMO, in concert with MORC3, orchestrates a metastable H3.3/H3K9me3 heterochromatin state on a multi-PU.1 binding platform element to shutdown unscheduled myeloid-specific IFN1 response.
Published in
Goffeney A, Hendriks IA, Morel V et al.
· Nucleic acids research 2025
· PMID 40744492
· doi:10.1093/nar/gkaf750
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE292571_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 116 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1240230 and SRA study SRP572195. Searching any of these in the dataset finder brings you back here.
Study design
15 conditions, mostly in duplicate
Serie4, BlaER1 WT Monocytes, DMSO, Input, ×4
Serie4, BlaER1 WT Monocytes, TAK, Input, ×4
Serie4, BlaER1 WT Monocytes, DMSO, ChIP MORC3, ×4
Serie1, RAW 264.7, Input, ×2
Serie1, RAW 264.7, 24h ML, Input, ×2
Serie1, RAW 264.7, 24h ML, ChIP H3.3, ×2
Serie2, RAW 264.7, Input, ×2
Serie2, RAW 264.7, ChIP Morc3, ×2
+11 more
Supports a between-group comparison across 36 samples.
15 replicated groups read from the first 40 of 116 sample titles; they account for 36 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8861632 Serie1, RAW 264.7, Input, REP1
- GSM8861633 Serie1, RAW 264.7, Input, REP2
- GSM8861634 Serie1, RAW 264.7, 24h ML, Input, REP1
- GSM8861635 Serie1, RAW 264.7, 24h ML, Input, REP2
- GSM8861636 Serie1,RAW 264.7, DMSO, ChIP H3.3, REP1
- GSM8861637 Serie1, RAW 264.7, DMSO, ChIP H3.3, REP2
- GSM8861638 Serie1, RAW 264.7, 24h ML, ChIP H3.3, REP1
- GSM8861639 Serie1, RAW 264.7, 24h ML, ChIP H3.3, REP2
- GSM8861640 Serie2, RAW 264.7, Input, REP1
- GSM8861641 Serie2, RAW 264.7, Input, REP2
- GSM8861642 Serie2, RAW 264.7, ChIP Morc3, REP1
- GSM8861643 Serie2, RAW 264.7, ChIP Morc3, REP2
- GSM8861644 Serie3, RAW 264.7, Input, REP1
- GSM8861645 Serie3, RAW 264.7, Input, REP2
- GSM8861646 Serie3, RAW 264.7, 24h ML, Input, REP1
- GSM8861647 Serie3, RAW 264.7, 24h ML, Input, REP2
- GSM8861648 Serie3, RAW 264.7, ChIP SUMO2/3, REP1
- GSM8861649 Serie3, RAW 264.7, ChIP SUMO2/3, REP2
- GSM8861650 Serie3, RAW 264.7, DMSO, ChIP H3K9me3, REP1
- GSM8861651 Serie3, RAW 264.7, DMSO, ChIP H3K9me3, REP2
- GSM8861652 Serie3, RAW 264.7, 24h ML, ChIP H3K9me3, REP1
- GSM8861653 Serie3, RAW 264.7, 24h ML, ChIP H3K9me3, REP2
- GSM8861654 Serie4, BlaER1 WT Monocytes, DMSO, Input, REP1
- GSM8861655 Serie4, BlaER1 WT Monocytes, DMSO, Input, REP2
- GSM8861656 Serie4, BlaER1 WT Monocytes, DMSO, Input, REP3
- GSM8861657 Serie4, BlaER1 WT Monocytes, DMSO, Input, REP4
- GSM8861658 Serie4, BlaER1 WT Monocytes, TAK, Input, REP1
- GSM8861659 Serie4, BlaER1 WT Monocytes, TAK, Input, REP2
- GSM8861660 Serie4, BlaER1 WT Monocytes, TAK, Input, REP3
- GSM8861661 Serie4, BlaER1 WT Monocytes, TAK, Input, REP4
- GSM8861662 Serie4, BlaER1 IFNAR Monocytes, Input, REP1
- GSM8861663 Serie4, BlaER1 IFNAR Monocytes, Input, REP2
- GSM8861664 Serie4, BlaER1 IFNAR_MORC3 Monocytes, Input, REP1
- GSM8861665 Serie4, BlaER1 IFNAR_MORC3 Monocytes, Input, REP2
- GSM8861666 Serie4, BlaER1 WT Monocytes, DMSO, ChIP MORC3, REP1
- GSM8861667 Serie4, BlaER1 WT Monocytes, DMSO, ChIP MORC3, REP2
- GSM8861668 Serie4, BlaER1 WT Monocytes, DMSO, ChIP MORC3, REP3
- GSM8861669 Serie4, BlaER1 WT Monocytes, DMSO, ChIP MORC3, REP4
- GSM8861670 Serie4, BlaER1 WT Monocytes, TAK, ChIP MORC3, REP1
- GSM8861671 Serie4, BlaER1 WT Monocytes, TAK, ChIP MORC3, REP2
+ 76 more — browse all 116 samples with per-sample file links →
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