GEO series

Epigenetic priming promotes acquisition of TKI resistance and oncogene amplification in human lung cancer [ChIP-seq 2]

GSE287156 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 24 samples Submitted 2025/02/26 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)
Samples: 24 samples: 12 conditions, mostly in duplicateGroups 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: Epigenetic priming promotes acquisition of tyrosine kinase inhibitor resistance and oncogene amplification in human lung cancerbioRxiv : the preprint server for biology · 2025

Summary (written by the submitters)

In mammalian cells, gene copy number is tightly controlled to maintain gene expression and genome stability. However, a near-universal molecular feature across cancer types is oncogene amplification, which promotes cancer progression by dramatically increasing the copy number and expression of tumor-promoting genes. For example, in tyrosine kinase inhibitor (TKI)-resistant lung adenocarcinoma (LUAD), oncogene amplification occurs in over 40% of patients’ tumors.

Read the full summary ↓

Despite the prevalence of oncogene amplification in TKI-resistant tumors, the mechanisms facilitating oncogene amplification are not fully understood. Here, we find that LUAD tumors exhibit a unique chromatin signature demarcated by strong CTCF and cohesin deposition in drug-naïve tumors, which correlates with the boundaries of oncogene amplicons in TKI-resistant LUAD cells. Throughout the acquisition of TKI resistance, we identified a global chromatin priming effect, marked by a dynamic increase of H3K27Ac, cohesin loading, and inter-TAD interactions, which occurs before the onset of oncogene amplification. Furthermore, we have identified that the protein METTL7A, which was previously reported to localize to the ER and inner nuclear membrane, has a novel chromatin regulatory function in binding to amplified oncogenes and regulating cohesin recruitment and inter-TAD interactions. Surprisingly, we discovered that METTL7A remodels the chromatin landscape prior to any noticeable oncogene copy number gains. Furthermore, while METTL7A depletion has little effect on drug-naïve cells, METTL7A depletion prevents the formation of TKI resistant-clones, highlighting the specific role of METTL7A as cells are acquiring resistance. In summary, we discovered an unexpected mechanism required for the acquisition of TKI resistance regulated by a largely uncharacterized factor, METTL7A. This discovery sheds new light into maintenance of oncogene copy number and paves the way to the development of new therapeutics for preventing TKI resistance in LUAD.

Published in

Epigenetic priming promotes acquisition of tyrosine kinase inhibitor resistance and oncogene amplification in human lung cancer

Starble RM, Sun EG, Gbyli R et al. · bioRxiv : the preprint server for biology 2025 · PMID 39974875 · doi:10.1101/2025.01.26.634826

This dataset

Open GSE287156 in finder → Find more human ChIP / ATAC / CUT&Tag datasets →

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 GSE287156_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 PRJNA1211505 and SRA study SRP557817. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39974875) ↗

Study design

12 conditions, mostly in duplicate

PC9_WT_input ×2 PC9_WT_MYC ×2 PC9_M7A_OE_input ×2 PC9_M7A_OE_MYC ×2 PC9_OR_WT_input ×2 PC9_OR_WT_MYC ×2 PC9_OR_M7A_OE_input ×2 PC9_OR_M7A_OE_MYC ×2 +4 more

Supports a between-group comparison across 24 samples.

How we read this: 12 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

GSM8740099 PC9_WT_input_rep1 PC9_WT_input
GSM8740100 PC9_WT_input_rep2 PC9_WT_input
GSM8740101 PC9_WT_MYC_rep1 PC9_WT_MYC
GSM8740102 PC9_WT_MYC_rep2 PC9_WT_MYC
GSM8740103 PC9_M7A_OE_input_rep1 PC9_M7A_OE_input
GSM8740104 PC9_M7A_OE_input_rep2 PC9_M7A_OE_input
GSM8740105 PC9_M7A_OE_MYC_rep1 PC9_M7A_OE_MYC
GSM8740106 PC9_M7A_OE_MYC_rep2 PC9_M7A_OE_MYC
GSM8740107 PC9_OR_WT_input_rep1 PC9_OR_WT_input
GSM8740108 PC9_OR_WT_input_rep2 PC9_OR_WT_input
GSM8740109 PC9_OR_WT_MYC_rep1 PC9_OR_WT_MYC
GSM8740110 PC9_OR_WT_MYC_rep2 PC9_OR_WT_MYC
GSM8740111 PC9_OR_M7A_OE_input_rep1 PC9_OR_M7A_OE_input
GSM8740112 PC9_OR_M7A_OE_input_rep2 PC9_OR_M7A_OE_input
GSM8740113 PC9_OR_M7A_OE_MYC_rep1 PC9_OR_M7A_OE_MYC
GSM8740114 PC9_OR_M7A_OE_MYC_rep2 PC9_OR_M7A_OE_MYC
GSM8740115 PC9_OR_K86A_input_rep1 PC9_OR_K86A_input
GSM8740116 PC9_OR_K86A_input_rep2 PC9_OR_K86A_input
GSM8740117 PC9_OR_K86A_MYC_rep1 PC9_OR_K86A_MYC
GSM8740118 PC9_OR_K86A_MYC_rep2 PC9_OR_K86A_MYC
GSM8740119 PC9_OR_EV_input_rep1 PC9_OR_EV_input
GSM8740120 PC9_OR_EV_input_rep2 PC9_OR_EV_input
GSM8740121 PC9_OR_EV_MYC_rep1 PC9_OR_EV_MYC
GSM8740122 PC9_OR_EV_MYC_rep2 PC9_OR_EV_MYC

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