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DOT1L shapes ncPRC1-target gene repression to maintain cell identity of DLBCL [RNA-Seq]

GSE327307 Homo sapiens (human) RNA-seq (gene expression) 24 samples Submitted 2026/06/19 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 24 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Topic
Diffuse large B-cell lymphomaThis series is part of our curated briefing on it.
Samples
24 samples: 8 conditions, mostly in triplicateGroups 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.
Summary (written by the submitters)
Germinal center (GC) B cell-like diffuse large B cell lymphoma (GCB-DLBCL) depends on the cooperative activity of the histone methyltransferases DOT1L and EZH2 to maintain its pro-proliferative GCB cell identity while repressing plasma cell (PC) differentiation. To explore the mechanisms underlying the co-dependency between DOT1L and EZH2 in GCB-DLBCL, we performed an EZH2 inhibition (EZH2i)-anchored genome-wide CRISPR interference screen and identified multiple candidate genes encoding components of non-canonical (nc) PRC1 complexes, including USP7, KDM2B, RING1, and PCGF1.
Read the full summary ↓
We identified USP7 as potential direct target of DOT1L, whose downregulation was associated with increased EZH2i sensitivity in multiple GCB-DLBCL cell lines. Furthermore, we observed that DOT1L influences the composition of chromatin-bound ncPRC1 complexes and regulates, in part, the deposition of H2AK119 monoubiquitination (H2AK119ub1) at gene promoters co-occupied by H3K27me3, here defined as PRC1/2 target genes. These PRC1/2 targets were specifically enriched in PC signature genes, whose derepression was associated with DOT1L inhibition (DOT1Li)-mediated loss of H2AK119ub1. This study reveals novel insights into the role of DOT1L and its functional co-dependence with EZH2 in maintaining GCB identity in DLBCL, supporting a model in which concurrent reduction of H2AK119ub1 and H3K27me3 promotes differentiation toward an anti-proliferative, plasma cell–like state.
This dataset
Open GSE327307 in finder → Find more human RNA-seq datasets → Diffuse large B-cell lymphoma landscape →
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 GSE327307_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1450390 and SRA study SRP690064. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
8 conditions, mostly in triplicate
SUDHL4_DMSO ×3 SUDHL4_DOT1Li ×3 SUDHL4_GSK343 ×3 SUDHL4_Combo ×3 SUDHL10_DMSO ×3 SUDHL10_DOT1Li ×3 WSU-DLCL2_DMSO ×3 WSU-DLCL2_DOT1Li ×3

Supports a between-group comparison across 24 samples.

How we read this: 8 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
More Diffuse large B-cell lymphoma datasets

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