GEO series
Sex-specific KDM6A-HNF4A-CREBH network controls lipoprotein cholesterol metabolism and atherosclerosis via epigenetic reprograming of hepatocytes
GSE287736
Homo sapiens; Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
138 samples
Submitted 2026/02/19
Platform GPL34290Platform GPL34284
Summary
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. 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
Chen L, Kang Z, Härdfeldt J et al.
· Nature communications 2026
· PMID 41872164
· doi:10.1038/s41467-026-70846-w
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE287736_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 138 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1214364 and SRA study SRP559280. Searching any of these in the dataset finder brings you back here.
Study design
12 conditions, mostly in triplicate
PCSK9_mice_WT_antiCREBH ×4
mice_flox_H3K4me1 ×3
mice_flox_H3K4me2 ×3
mice_flox_H3K27ac ×3
mice_flox_H3K27me3 ×3
mice_LKO_H3K4me1 ×3
mice_LKO_H3K4me2 ×3
mice_LKO_H3K27ac ×3
+8 more
Supports a between-group comparison across 36 samples.
12 replicated groups read from the first 40 of 138 sample titles; they account for 36 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8750625 mice_flox_H3K4me1_rep1
- GSM8750626 mice_flox_H3K4me1_rep2
- GSM8750627 mice_flox_H3K4me1_rep3
- GSM8750628 mice_flox_H3K4me2_rep1
- GSM8750629 mice_flox_H3K4me2_rep2
- GSM8750630 mice_flox_H3K4me2_rep3
- GSM8750631 mice_flox_H3K27ac_rep1
- GSM8750632 mice_flox_H3K27ac_rep2
- GSM8750633 mice_flox_H3K27ac_rep3
- GSM8750634 mice_flox_H3K27me3_rep1
- GSM8750635 mice_flox_H3K27me3_rep2
- GSM8750636 mice_flox_H3K27me3_rep3
- GSM8750637 mice_LKO_H3K4me1_rep1
- GSM8750638 mice_LKO_H3K4me1_rep2
- GSM8750639 mice_LKO_H3K4me1_rep3
- GSM8750640 mice_LKO_H3K4me2_rep1
- GSM8750641 mice_LKO_H3K4me2_rep2
- GSM8750642 mice_LKO_H3K4me2_rep3
- GSM8750643 mice_LKO_H3K27ac_rep1
- GSM8750644 mice_LKO_H3K27ac_rep2
- GSM8750645 mice_LKO_H3K27ac_rep3
- GSM8750646 mice_LKO_H3K27me3_rep1
- GSM8750647 mice_LKO_H3K27me3_rep2
- GSM8750648 mice_LKO_H3K27me3_rep3
- GSM8750649 HROhep03_input
- GSM8750650 Mice_input
- GSM9279040 Huh1_input
- GSM9279041 PCSK9_mice_input
- GSM9457753 HROHep03_siLuc_CREBH_rep1
- GSM9457754 HROHep03_siLuc_CREBH_rep2
- GSM9457755 HROHep03_siLuc_CREBH_rep3
- GSM9457756 HROHep03_siKDM6A_CREBH_rep1
- GSM9457757 HROHep03_siKDM6A_CREBH_rep2
- GSM9457758 HROHep03_siKDM6A_CREBH_rep3
- GSM9460724 PCSK9_mice_WT_antiCREBH_rep1
- GSM9460725 PCSK9_mice_WT_antiCREBH_rep2
- GSM9460726 PCSK9_mice_WT_antiCREBH_rep3
- GSM9460727 PCSK9_mice_WT_antiCREBH_rep4
- GSM9460728 PCSK9_mice_LKO_antiCREBH_rep1
- GSM9460729 PCSK9_mice_LKO_antiCREBH_rep2
+ 98 more — browse all 138 samples with per-sample file links →
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