GEO series
DOT1L provides transcriptional memory through PRC1.1 antagonism [RNA-seq]
GSE260456
Mus musculus; Homo sapiens
Expression profiling by high throughput sequencing
180 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
Smith CM, Venkataraman N, Gallagher MT et al.
· Nature 2003
· PMID 12904788
· doi:10.1038/nature01849
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE260456_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 180 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1081797 and SRA study SRP492287. Searching any of these in the dataset finder brings you back here.
Study design
10 conditions, mostly in triplicate
NTVKO PCGF1 KO DMSO ×3
NTVKO PCGF1 KO SGC0946 3uM ×3
NTVKO PCGF1 KO VTP50469 48h 300nM ×3
NTVKO PCGF1 KO VTP50469 8h 300nM ×3
NTVKO Control - DMSO ×3
NTVKO Control - SGC0946 3uM ×3
NTVKO Control - VTP50469 48h 300nM ×3
NTVKO Control - VTP50469 8h 300nM ×3
+14 more
Supports a between-group comparison across 28 samples.
10 replicated groups read from the first 40 of 180 sample titles; they account for 28 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8117469 NTVKO PCGF1 KO DMSO rep1
- GSM8117470 NTVKO PCGF1 KO SGC0946 3uM rep1
- GSM8117471 NTVKO PCGF1 KO VTP50469 48h 300nM rep1
- GSM8117472 NTVKO PCGF1 KO VTP50469 8h 300nM rep1
- GSM8117473 NTVKO Control - DMSO rep1
- GSM8117474 NTVKO Control - SGC0946 3uM rep1
- GSM8117475 NTVKO Control - VTP50469 48h 300nM rep1
- GSM8117476 NTVKO Control - VTP50469 8h 300nM rep1
- GSM8117477 NTVKO PCGF1 KO DMSO rep2
- GSM8117478 NTVKO PCGF1 KO SGC0946 3uM rep2
- GSM8117479 NTVKO PCGF1 KO VTP50469 48h 300nM rep2
- GSM8117480 NTVKO PCGF1 KO VTP50469 8h 300nM rep2
- GSM8117481 NTVKO Control - DMSO rep2
- GSM8117482 NTVKO Control - SGC0946 3uM rep2
- GSM8117483 NTVKO Control - VTP50469 48h 300nM rep2
- GSM8117484 NTVKO Control - VTP50469 8h 300nM rep2
- GSM8117485 NTVKO PCGF1 KO DMSO rep3
- GSM8117486 NTVKO PCGF1 KO SGC0946 3uM rep3
- GSM8117487 NTVKO PCGF1 KO VTP50469 48h 300nM rep3
- GSM8117488 NTVKO PCGF1 KO VTP50469 8h 300nM rep3
- GSM8117489 NTVKO Control - DMSO rep3
- GSM8117490 NTVKO Control - SGC0946 3uM rep3
- GSM8117491 NTVKO Control - VTP50469 48h 300nM rep3
- GSM8117492 NTVKO Control - VTP50469 8h 300nM rep3
- GSM8117493 PCGF1 KO Washout DMSO rep1
- GSM8117494 PCGF1 KO VTP50469 300nM 48+24w rep1
- GSM8117495 PCGF1 KO VTP50469 300nM 48+48w rep1
- GSM8117496 PCGF1 KO VTP50469 300nM 48+72w rep1
- GSM8117497 PCGF1 KO VTP50469 300nM 48h rep1
- GSM8117498 PCGF1 KO VTP50469 300nM 8+24w rep1
- GSM8117499 PCGF1 KO VTP50469 300nM 8h rep1
- GSM8117500 Control - Washout DMSO rep1
- GSM8117501 Control - VTP50469 300nM 48+24w rep1
- GSM8117502 Control - VTP50469 300nM 48+48w rep1
- GSM8117503 Control - VTP50469 300nM 48+72w rep1
- GSM8117504 Control - VTP50469 300nM 48h rep1
- GSM8117505 Control - VTP50469 300nM 8+24w rep1
- GSM8117506 Control - VTP50469 300nM 8h rep1
- GSM8117507 PCGF1 KO Washout DMSO rep2
- GSM8117508 PCGF1 KO VTP50469 300nM 48+24w rep2
+ 140 more — browse all 180 samples with per-sample file links →
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