GEO series

Sex-specific KDM6A-HNF4A-CREBH network controls lipoprotein cholesterol metabolism and atherosclerosis via epigenetic reprograming of hepatocytes [CUT&Tag]

GSE287680 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 22 samples Submitted 2026/02/19 Platform GPL34284

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 22 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: 22 samples: 6 conditions, mostly with about 4 replicates eachGroups 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: Sex-specific KDM6A-HNF4A-CREBH network controls lipoprotein cholesterol metabolism and atherosclerosis via epigenetic reprograming of hepatocytesNature communications · 2026

Summary (written by the submitters)

The liver is a central organ controlling lipid and cholesterol metabolism and plays a key role in regulating lipoprotein profiles and cardiovascular disease risk. Males and females show clear differences in cholesterol handling and susceptibility to atherosclerosis, but the molecular basis for these sex-specific effects remains incompletely understood.

Read the full summary ↓

Here we show that the X-linked histone demethylase 6A (KDM6A) is essential for maintaining healthy cholesterol metabolism in the liver. Reducing KDM6A levels in human liver cells disrupts gene programs involved in lipoprotein regulation linked to cardiovascular disorders. Consistently, female mice lacking KDM6A specifically in hepatocytes develops pro-atherogenic blood lipoprotein profiles and increased atherosclerosis under genetic and dietary stress, whereas males are largely unaffected. Mechanistically, KDM6A cooperates with Hepatocyte Nuclear Factor 4 Alpha (HNF4A) to promote chromatin activation and enable CREBH (encoded by CREB3L3)-dependent transcription of lipid metabolic genes. These findings identify KDM6A as a sex-linked regulator of hepatic cholesterol metabolism.

Published in

Sex-specific KDM6A-HNF4A-CREBH network controls lipoprotein cholesterol metabolism and atherosclerosis via epigenetic reprograming of hepatocytes

Chen L, Kang Z, Härdfeldt J et al. · Nature communications 2026 · PMID 41872164 · doi:10.1038/s41467-026-70846-w

This dataset

Open GSE287680 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 GSE287680_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 PRJNA1214240 and SRA study SRP559018. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41872164) ↗

Study design

6 conditions, mostly with about 4 replicates each

HRO_antiKDM6A_siluc ×4 HRO_antiKDM6A_siHNF4A ×4 Huh1_antiKDM6A_siluc ×4 Huh1_antiKDM6A_siHNF4A ×4 HUH7_antiKDM6A_siluc ×3 HUH7_antiKDM6A_siHNF4A ×3

Supports a between-group comparison across 22 samples.

How we read this: 6 replicated groups read from 22 sample titles; they account for 22 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

GSM8749771 HUH7_antiKDM6A_siluc_rep1 HUH7_antiKDM6A_siluc
GSM8749772 HUH7_antiKDM6A_siluc_rep2 HUH7_antiKDM6A_siluc
GSM8749773 HUH7_antiKDM6A_siluc_rep3 HUH7_antiKDM6A_siluc
GSM8749774 HUH7_antiKDM6A_siHNF4A_rep1 HUH7_antiKDM6A_siHNF4A
GSM8749775 HUH7_antiKDM6A_siHNF4A_rep2 HUH7_antiKDM6A_siHNF4A
GSM8749776 HUH7_antiKDM6A_siHNF4A_rep3 HUH7_antiKDM6A_siHNF4A
GSM9465091 HRO_antiKDM6A_siluc_rep1 HRO_antiKDM6A_siluc
GSM9465092 HRO_antiKDM6A_siluc_rep2 HRO_antiKDM6A_siluc
GSM9465093 HRO_antiKDM6A_siluc_rep3 HRO_antiKDM6A_siluc
GSM9465094 HRO_antiKDM6A_siluc_rep4 HRO_antiKDM6A_siluc
GSM9465095 HRO_antiKDM6A_siHNF4A_rep1 HRO_antiKDM6A_siHNF4A
GSM9465096 HRO_antiKDM6A_siHNF4A_rep2 HRO_antiKDM6A_siHNF4A
GSM9465097 HRO_antiKDM6A_siHNF4A_rep3 HRO_antiKDM6A_siHNF4A
GSM9465098 HRO_antiKDM6A_siHNF4A_rep4 HRO_antiKDM6A_siHNF4A
GSM9465099 Huh1_antiKDM6A_siluc_rep1 Huh1_antiKDM6A_siluc
GSM9465100 Huh1_antiKDM6A_siluc_rep2 Huh1_antiKDM6A_siluc
GSM9465101 Huh1_antiKDM6A_siluc_rep3 Huh1_antiKDM6A_siluc
GSM9465102 Huh1_antiKDM6A_siluc_rep4 Huh1_antiKDM6A_siluc
GSM9465103 Huh1_antiKDM6A_siHNF4A_rep1 Huh1_antiKDM6A_siHNF4A
GSM9465104 Huh1_antiKDM6A_siHNF4A_rep2 Huh1_antiKDM6A_siHNF4A
GSM9465105 Huh1_antiKDM6A_siHNF4A_rep3 Huh1_antiKDM6A_siHNF4A
GSM9465106 Huh1_antiKDM6A_siHNF4A_rep4 Huh1_antiKDM6A_siHNF4A

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