GEO series
SUMOylation enhances DNMT1 function to repress mega-intergenic RNAs and viral mimicry
GSE329512
Homo sapiens
Genome binding/occupancy profiling by high throughput sequencing
19 samples
Submitted 2026/05/17
Platform GPL30173
Summary
DNA methyltransferase 1 (DNMT1) is essential for mammalian development and is frequently dysregulated in cancer. While its recruitment to hemi-methylated DNA by UHRF1 is well established, its broader chromatin occupancy and regulation remain unclear. We show that DNMT1 is enriched at unmethylated CpG islands of actively transcribed genes largely by its CXXC domain. Upon selective catalytic inhibition, DNMT1 redistributes to partially methylated, inaccessible regions in a UHRF1- and RFTS-dependent manner. Despite minimal changes in coding gene expression, sustained DNMT1 inhibition and subsequent global DNA hypomethylation trigger reactivation of a previously uncharacterised class of dsRNA mega-intergenic transcripts (mintRNAs) driving a cell-intrinsic viral mimicry response. We identify RNF4 as a major regulator of DNMT1 catalytic function that, beyond its canonical role in DNA–protein crosslink resolution, controls the levels of SUMOylated DNMT1, establishing SUMOylation as a rheostat that regulates DNMT1 activity to maintain DNA methylation and safeguard against viral mimicry.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE329512_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 19 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1459374 and SRA study SRP696038. Searching any of these in the dataset finder brings you back here.
Study design
15 conditions, each sampled once — no replicated groups
MV411, gDNMT1, ectopic overexpression of GFP-… ×2
MV411, gDNMT1, ectopic overexpression of GFP-… ×2
MV411, gDNMT1, ectopic overexpression of GFP-… ×2
MV411, gDNMT1, ectopic overexpression of GFP-… ×2
Supports a case/control comparison: 4 samples read as cases, 1 as controls.
Read from 19 sample titles: 15 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9705309 MV411, gDNMT1, ectopic overexpression of GFP-tagged DNMT1 with CXXC domain deleted, DMSO for 7 days, rep 1
- GSM9705310 MV411, gDNMT1, ectopic overexpression of GFP-tagged DNMT1 with CXXC domain deleted, DMSO for 7 days, rep 2
- GSM9705311 MV411, gDNMT1, ectopic overexpression of GFP-tagged DNMT1 with CXXC domain deleted, DNMT1i for 7 days, rep 1
- GSM9705312 MV411, gDNMT1, ectopic overexpression of GFP-tagged DNMT1 with CXXC domain deleted, DNMT1i for 7 days, rep 2
- GSM9705313 MV411, gDNMT1, gNT, ectopic overexpression of GFP-tagged DNMT1 10KR mutant, DMSO for 7 days, rep 1
- GSM9705314 MV411, gDNMT1, gNT, ectopic overexpression of GFP-tagged DNMT1 10KR mutant, DNMT1i for 7 days, rep 1
- GSM9705315 MV411, gDNMT1, gRNF4, ectopic overexpression of GFP-tagged DNMT1 10KR mutant, DMSO for 7 days, rep 1
- GSM9705316 MV411, gDNMT1, gRNF4, ectopic overexpression of GFP-tagged DNMT1 10KR mutant, DNMT1i for 7 days, rep 1
- GSM9705317 MV411, gDNMT1, ectopic overexpression of GFP-tagged DNMT1 WT, DMSO for 7 days, rep 1
- GSM9705318 MV411, gDNMT1, ectopic overexpression of GFP-tagged DNMT1 WT, DMSO for 7 days, rep 2
- GSM9705319 MV411, gDNMT1, ectopic overexpression of GFP-tagged DNMT1 WT, DNMT1i for 7 days, rep 1
- GSM9705320 MV411, gDNMT1, ectopic overexpression of GFP-tagged DNMT1 WT, DNMT1i for 7 days, rep 2
- GSM9705321 MV411, gDNMT1, gNT, ectopic overexpression of GFP-tagged DNMT1 WT, DMSO for 7 days, rep 1
- GSM9705322 MV411, gDNMT1, gNT, ectopic overexpression of GFP-tagged DNMT1 WT, DNMT1i for 7 days, rep 1
- GSM9705323 MV411, gDNMT1, gRNF4, ectopic overexpression of GFP-tagged DNMT1 WT, DMSO for 7 days, rep 1
- GSM9705324 MV411, gDNMT1, gRNF4, ectopic overexpression of GFP-tagged DNMT1 WT, DNMT1i for 7 days, rep 1
- GSM9705325 Total gDNA input from library DNMT1-WT-DMSO-R1
- GSM9705326 Total gDNA input from library DNMT1-WT-gNT-DNMT1i-R1
- GSM9705327 Untreated, parental MV411 cells
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