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DOT1L-mediated H3K79me2 directs B-cell repertoire establishment, marginal zone development and germinal center function

GSE306634 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 21 samples Submitted 2025/09/01 Platform GPL30215Platform GPL16417Platform GPL30172
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 21 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
21 samples: 8 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-mediated H3K79me2 directs B-cell repertoire establishment, marginal zone development, and germinal center functionJournal of immunology (Baltimore, Md. : 1950) · 2026
Summary (written by the submitters)
DOT1L is an epigenetic regulator that promotes gene expression by methylating lysine 79 on histone H3 and recruits transcription factors to gene targets. DOT1L is also an oncogenic driver in cancers that affect developing lymphocytes, yet how DOT1L activity regulates B-cell maturation remains poorly defined. Here, we use deep-sequencing and conditional knockout models to elucidate gene targets of H3K79me2, and the mechanistic contribution of DOT1L, during key stages of murine B-cell development.
Read the full summary ↓
In the bone marrow, Dot1l was upregulated in pro B-cells. Deep-sequencing revealed that H3K79me2 accumulated during maturation. The genomic distribution of H3K79me2 peaks indicating that DOT1L regulates transcription and the cell cycle across different stages of B-cell development. As such, DOT1L was found to be essential for pre B-cell expansion, leading to a significant decrease in pre B-cells in the absence of DOT1L and a skewing of the B-cell receptor repertoire to favor proximal VH usage. In addition to the effective generation of a diverse B-cell pool, DOT1L was also required to establish the marginal zone (MZ) B-cell gene expression program. Attenuation of MZ B-cells and a bottlenecking at the pre-MZ B-cell stage in Dot1L-deficient mice correlated to H3K79me2 peaks at key MZ-regulatory genes such as Lfng and Dock10 in developing B cells. In contrast, Dot1l was re-expressed in germinal center (GC) B-cells post-immunization to deposit H3K79me2 at key GC B-cell gene loci during GC differentiation. Together, these data demonstrate a vital role for DOT1L during B cell lymphopoiesis, MZ B-cell generation and GC B-cell biology.
Published in
DOT1L-mediated H3K79me2 directs B-cell repertoire establishment, marginal zone development, and germinal center function
Kealy LC, Russ BE, Turner SJ et al. · Journal of immunology (Baltimore, Md. : 1950) 2026 · PMID 40972012 · doi:10.1093/jimmun/vkaf243
This dataset
Open GSE306634 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 GSE306634_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 PRJNA1311542 and SRA study SRP613654. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40972012) ↗
Study design
8 conditions, mostly in duplicate
Follicular B cells from Cre control mice, BCR… ×3 Follicular B cells from Dot1l conditional kno… ×3 Developing B cells (B220+IgD-IgM-CD24+) isola… ×2 Developing B cells (B220+IgD-IgM-CD24+) isola… ×2 Naïve B cells (CD19+IgD+) isolated from naïve… ×2 Naïve B cells (CD19+IgD+) isolated from naïve… ×2 Germinal center B cells (CD19+IgD-CD95+CD38-C… ×2 Germinal center B cells (CD19+IgD-CD95+CD38-C… ×2 +3 more

Supports a case/control comparison: 3 samples read as cases, 11 as controls.

How we read this: 8 replicated groups read from 21 sample titles; they account for 18 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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