GEO series

The histone-methyltransferase DOT1L cooperates with LSD1 to control cell division in blast-phase MPN [ChIP-seq]

GSE300505 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 37 samples Submitted 2025/07/29 Platform GPL34284

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 37 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: Homo sapiens (human)
Topic: Myeloproliferative neoplasmsThis series is part of our curated briefing on it.
Samples: 37 samples: 27 distinct titles, 7 of them repeatedGroups 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: The histone-methyltransferase DOT1L cooperates with LSD1 to control cell division in blast-phase MPNLeukemia · 2025

Summary (written by the submitters)

Persistence of JAK2-mutated clones that may undergo clonal evolution and malignant transformation remains a challenge in myeloproliferative neoplasms (MPN), Novel therapeutic approaches to attenuate clonal evolution and progression to blast-phase are therefore urgently needed. LSD1 (KDM1A) inhibitors reduce symptoms and clonal burden in MPN, but whether these compounds may be effective in advanced disease stages remained so far elusive.

Read the full summary ↓

Using a chromatin-focused CRISPR-Cas9 screen, we identified the histone methyltransferase DOT1L as a synthetic lethal target under pharmacologic LSD1 inhibition. DOT1L knockout impaired cellular fitness, reduced proliferation, and prolonged survival in xenografts. Furthermore, genetic inactivation of DOT1L increased LSD1 inhibitor sensitivity up to 100-fold resulting in cell cycle arrest and apoptosis induction in TP53 mutant blast-phase MPN. Mechanistically, we have identified a novel, non-canonical function of DOT1L which co-occupied LSD1-bound enhancers and contributed to the repression of transcriptional programs independent of its enzymatic activity. DOT1L loss cooperated with LSD1 inhibitors to activate tumor suppressive programs, while pharmacologic inhibition of DOT1Ls catalytic activity failed to elicit comparable effects. These findings indicate that leveraging DOT1L targeting via protein degradation or RNA interference, rather than conventional enzymatic inhibition, could enhance the therapeutic efficacy of LSD1 inhibitors in blast-phase MPN.

Published in

The histone-methyltransferase DOT1L cooperates with LSD1 to control cell division in blast-phase MPN

Kapahnke K, Plenge T, Klaus T et al. · Leukemia 2025 · PMID 40781484 · doi:10.1038/s41375-025-02719-y

This dataset

Open GSE300505 in finder → Find more human ChIP / ATAC / CUT&Tag datasets → Myeloproliferative neoplasms 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 GSE300505_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 PRJNA1281077 and SRA study SRP593920. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40781484) ↗

Study design

27 distinct titles, 7 of them repeated

Exp.1_HEL_DOT1L-ChIP ×3 Exp.1_HEL_H3K79me2-ChIP ×3 Exp.1_HEL_LSD1-ChIP ×3 Exp.1_HEL_H3K4me1-ChIP ×2 Exp.2_SET2_DOT1L-ChIP ×2 Exp.2_SET2_H3K4me1-ChIP ×2 Exp.2_SET2_H3K79me2-ChIP ×2

How we read this: Read from 37 sample titles: 27 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

GSM9063513 Exp.1_HEL_DOT1L-ChIP-rep1
GSM9063514 Exp.1_HEL_DOT1L-ChIP-rep2
GSM9063515 Exp.1_HEL_DOT1L-ChIP-rep3
GSM9063516 Exp.1_HEL_H3K4me1-ChIP-rep1
GSM9063517 Exp.1_HEL_H3K4me1-ChIP-rep2
GSM9063518 Exp.1_HEL_H3K79me2-ChIP-rep1
GSM9063519 Exp.1_HEL_H3K79me2-ChIP-rep2
GSM9063520 Exp.1_HEL_H3K79me2-ChIP-rep3
GSM9063521 Exp.1_HEL_LSD1-ChIP-rep1
GSM9063522 Exp.1_HEL_LSD1-ChIP-rep2
GSM9063523 Exp.1_HEL_LSD1-ChIP-rep3
GSM9063524 Exp.1_HEL_input_chromatin
GSM9063525 Exp.2_SET2_DOT1L-ChIP_rep1
GSM9063526 Exp.2_SET2_DOT1L-ChIP_rep2
GSM9063527 Exp.2_SET2_H3K4me1-ChIP_rep1
GSM9063528 Exp.2_SET2_H3K4me1-ChIP_rep2
GSM9063529 Exp.2_SET2_H3K79me2-ChIP_rep1
GSM9063530 Exp.2_SET2_H3K79me2-ChIP_rep2
GSM9063531 Exp.2_SET2_input_chromatin
GSM9063532 Exp.3_MOLM13_DOT1L-ChIP
GSM9063533 Exp.3_MOLM13_H3K79me2-ChIP
GSM9063534 Exp.3_MOLM13_input-chromatin
GSM9063535 Exp.4_HEL_DOT1L-ko_LSD1-ChIP
GSM9063536 Exp.4_HEL_NTC_input_chromatin
GSM9063537 Exp.4_HEL_NTC_LSD1-ChIP
GSM9063538 Exp.5_patient_MPN-BP1_input-chromatin
GSM9063539 Exp.5_patient_MPN-BP1_LSD1-ChIP
GSM9063540 Exp.5_patient_MPN-BP1_DOT1L-ChIP
GSM9063541 Exp.5_patient_MPN-BP2_input-chromatin
GSM9063542 Exp.5_patient_MPN-BP2_LSD1-ChIP
GSM9063543 Exp.5_patient_MPN-BP2_DOT1L-ChIP
GSM9063544 Exp.5_patient_MPN-BP4_input-chromatin
GSM9063545 Exp.5_patient_MPN-BP4_LSD1-ChIP
GSM9063546 Exp.5_patient_MPN-BP4_DOT1L-ChIP
GSM9063547 Exp.5_patient_MPN-BP5_input-chromatin
GSM9063548 Exp.5_patient_MPN-BP5_LSD1-ChIP
GSM9063549 Exp.5_patient_MPN-BP5_DOT1L-ChIP

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GSE300470 A Stem and Progenitor Cell-Derived Gene Expression Signature is Prognostic for Survival in Myelofibrosis [RNA-Seq] 358 samples same disease briefing
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