GEO series

DOT1L provides transcriptional memory through PRC1.1 antagonism [ChIP-Seq]

GSE260742 Homo sapiens; Mus musculus Genome binding/occupancy profiling by high throughput sequencing 158 samples Submitted 2025/11/23 Platform GPL24676Platform GPL24247

Summary

DOT1L and Menin are essential cofactors for the oncogenic activity of MLL-fusion proteins (MLL-FPs) in leukaemia. However, the mechanisms underpinning the therapeutic effects of their inhibitors remain unclear. Here, we identify a critical role for the non-canonical Polycomb repressive complex 1.1 (PRC1.1) in mediating the cellular responses to DOT1L and Menin inhibitors. Menin inhibition induces PRC1.1-dependent deposition of H2AK119ub to silence a subset of MLL-FP targets, whereas DOT1L inhibition results in a genome-wide increase in H2AK119ub. We show that enhanced PRC1.1 activity arises specifically from the progressive loss of DOT1L-mediated H3K79 methylation, independent of MLL-FP displacement or transcriptional repression. This regulatory crosstalk is conserved across cell types and is driven by direct biochemical antagonism between H3K79 methylation and PRC1.1 activity. Together, our findings establish DOT1L as a component of transcriptional memory co-opted in leukaemia and suggest it serves as the missing link balancing the opposing forces of the MLL-Polycomb system.

Published in

Low-loss hollow-core silica/air photonic bandgap fibre

Smith CM, Venkataraman N, Gallagher MT et al. · Nature 2003 · PMID 12904788 · doi:10.1038/nature01849

This dataset

Open GSE260742 in finder → Find more ChIP / ATAC / CUT&Tag datasets →

Download

Direct links to NCBI, no account and no request form: the whole study as GSE260742_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 158 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1083204 and SRA study SRP493030. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 12904788) ↗

Study design

36 conditions, each sampled once — no replicated groups

MLLAF9 Control - DMSO input ×2 MLLAF9 Control - DMSO H2AK119ub ×2 MLLAF9 Control - SGC0946 5uM H2AK119ub ×2 MLLAF9 Control - VTP50469 500nM H2AK119ub ×2

Read from the first 40 of 158 sample titles: 36 distinct titles with little repetition. Check it against the sample list below before relying on it.

Similar datasets

Search all ChIP / ATAC / CUT&Tag datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.