GEO series
The PML1-WDR5 axis regulates H3K4me3 marks and promotes stemness of estrogen receptor-positive breast cancer
GSE255018
Homo sapiens (human)
ChIP-seq / ATAC-seq (genome binding and open chromatin)
24 samples
Submitted 2024/04/12
Platform GPL24676
At a glance
ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 24 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
- Breast cancerThis series is part of our curated briefing on it.
- Samples
- 24 samples: 6 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.
- Paper
- The PML1-WDR5 axis regulates H3K4me3 marks and promotes stemness of estrogen receptor-positive breast cancerCell death and differentiation · 2024
Summary (written by the submitters)
The alternative splicing of PML precursor mRNA gives rise to various PML isoforms, yet their expression profile in breast cancer cells remains uncharted. We discovered that PML1 is the most abundant isoform in all breast cancer subtypes, and its expression is associated with unfavorable prognosis in estrogen receptor-positive (ER+) breast cancers.
Read the full summary ↓
PML depletion reduces cell proliferation, invasion, and stemness, while heterologous PML1 expression augments these processes and fuels tumor growth and resistance to fulvestrant, an FDA-approved drug for ER+ breast cancer, in a mouse model. Moreover, PML1, rather than the well-known tumor suppressor isoform PML4, rescues the proliferation of PML knockdown cells. ChIP-seq analysis reveals significant overlap between PML-, ER-, and Myc-bound promoters, suggesting their coordinated regulation of target gene expression, including genes involved in breast cancer stem cells (BCSCs), such as JAG1, KLF4, YAP1, SNAI1, and MYC. Loss of PML reduces BCSC-related gene expression, and exogenous PML1 expression elevates their expression. Consistently, PML1 restores the association of PML with these promoters in PML-depleted cells. We identified a novel association between PML1 and WDR5, a key component of H3K4 methyltransferase (HMTs) complexes that catalyze H3K4me1 and H3K4me3. ChIP-seq analyses showed that the loss of PML1 reduces H3K4me3 in numerous loci, including BCSC-associated gene promoters. Additionally, PML1, not PML4, re-establishes the H3K4me3 mark on these promoters in PML-depleted cells. Significantly, PML1 is essential for recruiting WDR5, MLL1, and MLL2 to these gene promoters. Inactivating WDR5 by knockdown or inhibitors phenocopies the effects of PML1 loss, reducing BCSC-related gene expression and tumorsphere formation and enhancing fulvestrant’s anticancer activity. Our findings challenge the conventional understanding of PML as a tumor suppressor, redefine its role as a promoter of tumor growth in breast cancer and offer new insights into the unique roles of PML isoforms in breast cancer.
Published in
Pai CP, Wang H, Seachrist DD et al.
· Cell death and differentiation 2024
· PMID 38627584
· doi:10.1038/s41418-024-01294-6
This dataset
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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.
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 GSE255018_RAW.tar (it can run to tens of gigabytes).
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.
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 PRJNA1073211 and SRA study SRP488030. Searching any of these in the dataset finder brings you back here.
Study design
6 conditions, mostly in triplicate
MCF7, H3K4me3, shCtrl, ×3
MCF7, H3K4me3, shPML#1, ×3
MCF7, H3K4me3, shPML#2, ×3
ZR75, PML, ×3
ZR75, H3K4me3, shPML#2, ×3
ZR75, H3K4me3, shCtrl, ×3
MCF7, H3K4me3, shCtrl, input ×1
MCF7, H3K4me3, shPML#1, input ×1
+4 more
Supports a between-group comparison across 18 samples.
How we read this: 6 replicated groups read from 24 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
- GSM8062627 MCF7, H3K4me3, shCtrl, rep1 MCF7, H3K4me3, shCtrl,
- GSM8062628 MCF7, H3K4me3, shCtrl, rep2 MCF7, H3K4me3, shCtrl,
- GSM8062629 MCF7, H3K4me3, shCtrl, rep3 MCF7, H3K4me3, shCtrl,
- GSM8062630 MCF7, H3K4me3, shCtrl, input
- GSM8062631 MCF7, H3K4me3, shPML#1, rep1 MCF7, H3K4me3, shPML#1,
- GSM8062632 MCF7, H3K4me3, shPML#1, rep2 MCF7, H3K4me3, shPML#1,
- GSM8062633 MCF7, H3K4me3, shPML#1, rep3 MCF7, H3K4me3, shPML#1,
- GSM8062634 MCF7, H3K4me3, shPML#1, input
- GSM8062635 MCF7, H3K4me3, shPML#2, rep1 MCF7, H3K4me3, shPML#2,
- GSM8062636 MCF7, H3K4me3, shPML#2, rep2 MCF7, H3K4me3, shPML#2,
- GSM8062637 MCF7, H3K4me3, shPML#2, rep3 MCF7, H3K4me3, shPML#2,
- GSM8062638 MCF7, H3K4me3, shPML#2, input
- GSM8062639 ZR75, PML, rep1 ZR75, PML,
- GSM8062640 ZR75, PML,rep2 ZR75, PML,
- GSM8062641 ZR75, PML,rep3 ZR75, PML,
- GSM8062642 ZR75, H3K4me3, shPML#2, rep1 ZR75, H3K4me3, shPML#2,
- GSM8062643 ZR75, H3K4me3, shPML#2, rep2 ZR75, H3K4me3, shPML#2,
- GSM8062644 ZR75, H3K4me3, shPML#2, rep3 ZR75, H3K4me3, shPML#2,
- GSM8062645 ZR75, H3K4me3, shPML#2, input
- GSM8062646 ZR75, H3K4me3, shCtrl, rep1 ZR75, H3K4me3, shCtrl,
- GSM8062647 ZR75, H3K4me3, shCtrl, rep2 ZR75, H3K4me3, shCtrl,
- GSM8062648 ZR75, H3K4me3, shCtrl, rep3 ZR75, H3K4me3, shCtrl,
- GSM8062649 ZR75, H3K4me3, shCtrl, input
- GSM8062650 ZR75, PML, input
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