GEO series

DNMT1 loss leads to hypermethylation of a subset of late replicating domains by DNMT3A (RNA-seq)

GSE319745 Homo sapiens (human) DNA methylation 10 samples Submitted 2026/03/26 Platform GPL24676

At a glance

DNA methylation · human · 10 samples

What it is: DNA methylationChemical marks on DNA that help switch genes on or off.
Organism: Homo sapiens (human)
Samples: 10 samples: 10 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.
Paper: DNMT1 loss leads to hypermethylation of a subset of late replicating domains by DNMT3APLoS genetics · 2026

Summary (written by the submitters)

Loss of DNA methylation is a hallmark of cancer that is proposed to promote carcinogenesis through gene expression alterations, retrotransposon activation and induction of genomic instability. Cancer-associated hypomethylation does not occur across the whole genome but leads to the formation of partially methylated domains (PMDs). However, the mechanisms underpinning PMD formation remain unclear.

Read the full summary ↓

PMDs replicate late in S-phase leading to the proposal that they become hypomethylated due to incomplete re-methylation by the maintenance methyltransferase DNMT1 during cell division. Here we investigate the role of DNMT1 in the formation of PMDs in cancer by conducting whole genome bisulfite sequencing (WGBS), repli-seq and ChIP-seq on DNMT1 knockout HCT116 colorectal cancer cells (DNMT1 KO cells). We find that DNMT1 loss leads to preferential hypomethylation in late replicating, heterochromatic PMDs marked by the constitutive heterochromatic mark H3K9me3 or the facultative heterochromatic mark H3K27me3. However, we also observe that a subset of H3K9me3-marked PMDs gain methylation in DNMT1 KO cells. We find that, in DNMT1 KO cells, these hypermethylated PMDs remain late replicating but gain DNMT3A localisation. This is accompanied by loss of heterochromatic H3K9me3 and specific gain of euchromatic H3K36me2. Our observations suggest that hypermethylated PMDs lose their heterochromatic state, enabling their methylation by DNMT3A and the establishment of a hypermethylated, non-PMD state, despite their late replication timing. More generally, our findings suggest that the de novo DNMTs play a key role in establishing domain level DNA methylation patterns in cancer cells.

Published in

DNMT1 loss leads to hypermethylation of a subset of late replicating domains by DNMT3A

Kafetzopoulos I, Taglini F, Pasquier M et al. · PLoS genetics 2026 · PMID 41926459 · doi:10.1371/journal.pgen.1012098

This dataset

Open GSE319745 in finder → Find more human RNA-seq 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 GSE319745_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 beta-value tables or raw IDAT files among the supplementary files.

Also filed as BioProject PRJNA1425043 and SRA study SRP677810. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41926459) ↗

Study design

10 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 10 sample titles: 10 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

GSM9525670 HCT116_rep_1_RNA-seq
GSM9525671 HCT116_rep_2_RNA-seq
GSM9525672 HCT116_rep_3_RNA-seq
GSM9525673 HCT116_rep_7_RNA-seq
GSM9525674 HCT116_rep_8_RNA-seq
GSM9525675 HCT116_rep_9_RNA-seq
GSM9525676 DNMT1_KO_rep_1_RNA_seq
GSM9525677 DNMT1_KO_rep_2_RNA_seq
GSM9525678 DNMT1_KO_rep_3_RNA_seq
GSM9525679 DNMT1_KO_rep_4_RNA_seq

Datasets on a similar topic

GSE297847 DNMT1 loss leads to hypermethylation of a subset of late replicating domains by DNMT3A. 42 samples shares dnmt3a, dnmt1, hypermethylation, replicating, domains, subset, leads
GSE297781 DNMT1 loss leads to hypermethylation of a subset of late replicating domains by DNMT3A (histone ChIP-seq) 14 samples shares dnmt3a, dnmt1, hypermethylation, replicating, domains, subset, leads
GSE297779 DNMT1 loss leads to hypermethylation of a subset of late replicating domains by DNMT3A (H3K36me2 native ChIP-seq) 8 samples shares dnmt3a, dnmt1, hypermethylation, replicating, domains, subset, leads
GSE63280 Targeted disruption of DNMT1, 3A and 3B in human embryonic stem cells [DNMT3A/3B DKO] 8 samples shares dnmt3a, dnmt1
GSE284387 DNMT1 RFTS mutation alters RNA splicing and drives neurodegeneration via its RNA-binding function [RNA-Seq] 26 samples shares dnmt1, rna-seq
GSE337276 DNA methylation maintenance by DNMT1 is essential for human trophoblast stem cell homeostasis and differentiation [RNA-seq] 15 samples shares dnmt1, rna-seq
GSE308271 DNMT3A:R882H Is Not Required for Disease Maintenance in Primary Human AML, but Is Associated With Increased Leukemia Stem Cell Frequency [RNA-Seq] 14 samples shares dnmt3a, rna-seq
GSE305298 RNA-seq data from human HCT116 wild-type cells, HCT116 DNMT1 hypomorphs, and HCT116 UHRF1 hypomorphs. 8 samples shares dnmt1, rna-seq

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