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DOT1L activity limits transcription elongation velocity and favors RNAPII pausing to facilitate mutagenesis by AID. [ChIP-seq]

GSE290944 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 24 samples Submitted 2025/11/13 Platform GPL24247
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 24 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
24 samples: 12 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
DOT1L activity limits transcription elongation velocity and favors RNAPII pausing to facilitate mutagenesis by AIDNature communications · 2026
Summary (written by the submitters)
Activation-induced deaminase (AID) initiates class switch recombination (CSR) and somatic hypermutation of immunoglobulin genes, which are required for efficient antibody responses. Collaterally, AID can also mutate a set of off-target genes with oncogenic consequences. The mechanisms that make such loci susceptible to AID are not fully understood.
Read the full summary ↓
We find that the H3K79 histone methyltransferase DOT1L is located close to AID in the nucleus. Not only does DOT1L activity facilitate CSR, but it also facilitates AID off-target activity, including Igh-cMyc translocations. Genes mutated by AID display high DOT1L activity. DOT1L deficiency causes mostly increased nascent transcription, accompanied by a modest reduction in RNAPII occupancy. By integrating different genomic approaches, we discovered that DOT1L restricts the velocity of transcription elongation proportionally to the level of higher order H3K79 methylation (H3K79me2/3) and favors RNAPII pausing. These transcriptional conditions enhance AID occupancy and, consequently, its activity. Our data indicate a role for DOT1L and H3K79me2/3 in limiting transcription and highlight stronger RNAPII pausing and attenuated RNAPII elongation velocity as critical steps for productive AID association and mutagenesis at target loci. Furthermore, increased transcription elongation velocity could explain both upregulation and downregulation of genes in DOT1L-deficient cells.
Published in
DOT1L activity limits transcription elongation velocity and favors RNAPII pausing to facilitate mutagenesis by AID
Subramani PG, Seija N, Ridani J et al. · Nature communications 2026 · PMID 41526379 · doi:10.1038/s41467-026-68332-4
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 GSE290944_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 PRJNA1231055 and SRA study SRP567617. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41526379) ↗
Study design
12 conditions, mostly in duplicate
H3K79me2 ×2 H3K79me3 ×2 Rad21_WT ×2 Rad21_Dot1l_KO ×2 Nipbl_WT ×2 Nipbl_Dot1l_KO ×2 RNAPII_WT ×2 RNAPII_Dot1l_KO ×2 +4 more

Supports a between-group comparison across 24 samples.

How we read this: 12 replicated groups read from 24 sample titles; they account for 24 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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