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

GSE287736 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 138 samples Submitted 2026/02/19 Platform GPL34290Platform GPL34284
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 138 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
138 samples: 36 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 GSE287736 in finder → Find more 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 GSE287736_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 PRJNA1214364 and SRA study SRP559280. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41872164) ↗
Study design
36 conditions, mostly with about 4 replicates each
PCSK9_mice_WT_antiCREBH ×4 PCSK9_mice_LKO_antiCREBH ×4 HROhep03_siLuc_H3K4me1 ×4 HROhep03_siKDM6A_H3K4me1 ×4 HROhep03_siHNF4A_H3K4me1 ×4 HROhep03_siLuc_H3K4me2 ×4 HROhep03_siKDM6A_H3K4me2 ×4 HROhep03_siHNF4A_H3K4me2 ×4 +32 more

Supports a between-group comparison across 134 samples.

How we read this: 36 replicated groups read from 138 sample titles; they account for 134 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

+ 98 more — browse all 138 samples with per-sample file links →

Datasets on a similar topic

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