GEO series

Lactylation of LSD1 is an acquired epigenetic vulnerability of BRAFi/MEKi-resistant melanoma [ChIP-seq]

GSE256123 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 14 samples Submitted 2025/02/13 Platform GPL20795

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 14 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: MelanomaThis series is part of our curated briefing on it.
Samples: 14 samples: 14 samples, each with a distinct title — no replicated groupsGroups 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.

Summary (written by the submitters)

BRAFV600E mutant melanomas treated with BRAF inhibitor (Dabrafenib) and MEK inhibitor (Trametinib) almost invariably develop drug resistance (DTR). Restored glycolysis, frequently found in clinical targeted therapy-resistant melanoma biopsies, has been shown to elicit drug resistance. How resumed glycolysis controls the emergence of acquired resistance, especially via intrinsic mechanisms that circumvent the BRAF/MEK module, remains unknown.

Read the full summary ↓

Here, we identify lactylation of LSD1, induced by re-accumulated lactate in DTR melanoma cells, selectively drives survival via epigenetic reprogramming. Mechanistically, lactylation of LSD1 promotes its interaction with FosL1, thereby preventing its ubiquitination and degradation by E3 ligase tripartite-motif-containing protein 21 (TRIM21). In DTR melanoma cells, chromatin binding capacity of FosL1 was significantly strengthened due to reduced acetylation, which in turn increases selective chromatin enrichment of LSD1. We further demonstrate that lactylated LSD1 co-orchestrates gene transcription with FosL1 to repress ferroptosis in DTR cells via interfering with transferrin receptor protein 1 (TFRC)-mediated iron uptake. LSD1 inhibitor (LSD1i) activates ferroptosis, resulting in drastic DTR melanoma regression in mice. Importantly, LSD1i-induced immunogenic ferroptosis synergizes with immune checkpoint blockade (ICB) in vivo. Together, our results highlight a crucial role of metabolic rewiring-induced epigenetic reprogramming as a bypass resistance mechanism in DTR melanoma, which provides a therapeutically actionable strategy to overcome acquired resistance to targeted therapy.

This dataset

Open GSE256123 in finder → Find more human ChIP / ATAC / CUT&Tag datasets → Melanoma 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 GSE256123_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 PRJNA1078295 and SRA study SRP490654. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

14 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 14 sample titles: 14 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

GSM8086108 ChIP_seq_LSD1_P
GSM8086109 ChIP_seq_LSD1_R
GSM8086110 ChIP_seq_LSD1_R_KDT21ctl
GSM8086111 ChIP_seq_LSD1_R_KDT21_fosl1
GSM8086112 ChIP_seq_H3K4me2_P
GSM8086113 ChIP_seq_H3K4me2_R
GSM8086114 ChIP_seq_H3K4me2_R_KDT21_ctl
GSM8086115 ChIP_seq_H3K4me2_R_KDT21_fosl1
GSM8086116 ChIP_seq_FosL1_P
GSM8086117 ChIP_seq_FosL1_R
GSM8086118 ChIP_FosL1_CTL
GSM8086119 ChIP_FosL1_KDL1
GSM8086120 ChIP_FosL1_WT
GSM8086121 ChIP_FosL1_K116Q

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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.