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Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch [ChIP-seq]

GSE247015 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 10 samples Submitted 2024/08/31 Platform GPL21626
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 10 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
Mus musculus (mouse)
Samples
10 samples: 5 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
Cancer-associated DNA hypermethylation of Polycomb targets requires DNMT3A dual recognition of histone H2AK119 ubiquitination and the nucleosome acidic patchScience advances · 2024
Summary (written by the submitters)
During tumor development, promoter CpG islands (CGIs) that are normally silenced by Polycomb repressive complexes (PRCs) become DNA hypermethylated. The molecular mechanism by which de novo DNA methyltransferase(s) catalyze CpG methylation at PRC-regulated regions remains unclear. Here we report a cryo-EM structure of DNMT3A long isoform (DNMT3A1) N-terminal region in complex with nucleosome carrying PRC1-mediated histone H2A lysine 119 mono-ubiquitination (H2AK119Ub).
Read the full summary ↓
We identify regions within the DNMT3A1 N-terminus that bind H2AK119Ub and the nucleosome acidic patch. This bidentate interaction is specifically required for effective DNMT3A1 engagement with H2AK119Ub-modified chromatin in cells. Furthermore, aberrant redistribution of DNMT3A1 to Polycomb target genes inhibits their transcriptional derepression during cell differentiation and recapitulates the cancer-associated DNA hypermethylation signature, an effect rescued by disruption of DNMT3A1-acidic patch interaction. Together, our analyses reveal a binding interface critical for countering promoter CGI DNA hypermethylation, a major molecular hallmark of cancer.
Published in
Cancer-associated DNA hypermethylation of Polycomb targets requires DNMT3A dual recognition of histone H2AK119 ubiquitination and the nucleosome acidic patch
Gretarsson KH, Abini-Agbomson S, Gloor SL et al. · Science advances 2024 · PMID 39196936 · doi:10.1126/sciadv.adp0975
This dataset
Open GSE247015 in finder → Find more mouse 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 GSE247015_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 PRJNA1035557 and SRA study SRP470145. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39196936) ↗
Study design
5 conditions, mostly in duplicate
QKO, DNMT3A WT, DNMT3A ChIP ×2 QKO, DNMT3A W330R, DNMT3A ChIP ×2 QKO, DNMT3A R181E, DNMT3A ChIP ×2 QKO, DNMT3A UBmutant, DNMT3A ChIP ×2 QKO, DNMT3A WT, Input ChIP ×2

Supports a case/control comparison: 2 samples read as cases, 4 as controls.

How we read this: 5 replicated groups read from 10 sample titles; they account for 10 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
Datasets on a similar topic

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