ArticleMolecular and cellular biology2021
STAT5 Regulation of Sex-Dependent Hepatic CpG Methylation at Distal Regulatory Elements Mapping to Sex-Biased Genes.
Article in Molecular and cellular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 28 citations in OpenAlex.
- Disease-associated mutations in the STAT5B SH2 domain reprogram hepatic cholesterol and lipid metabolism.Endocrinology · 2026Article
- KDM5C and KDM5D influence DNA methylation in adult mouse liver.Biology of sex differences · 2026Article
- HDI-STARR-seq Identifies Functional GH-regulated Sex-Biased Hepatocyte Enhancers Linked to Liver Metabolism and Disease.bioRxiv : the preprint server for biology · 2026Article
- GH-resistant (Laron) mice: gene therapy with a liver-specific GH receptor causes unbalanced upregulation of female-biased and growth-related genes.Frontiers in endocrinology · 2026Article
- Disease-associated mutations in the STAT5B SH2 domain reprogram hepatic cholesterol and lipid metabolism.bioRxiv : the preprint server for biology · 2025Article
- Single Nucleus MultiOmics Links Novel Transcription Factor Motifs to Murine Hepatic Sex Differences in Chromatin Accessibility and Metabolic Dysfunction-Associated Steatotic Liver Disease.bioRxiv : the preprint server for biology · 2025Article
- Cross-tissue molecular responses in the liver and blood after toxicant exposures.Research square · 2025Article
- Survey of gene, lncRNA and transposon transcription patterns in four mouse organs highlights shared and organ-specific sex-biased regulation.Genome biology · 2025Article
- Liver-specific actions of GH and IGF1 that protect against MASLD.Nature reviews. Endocrinology · 2025 · on this mapReview
- Hepatic estrogen receptor alpha drives masculinization in post-menopausal women with metabolic dysfunction-associated steatotic liver disease.JHEP reports : innovation in hepatology · 2024Article
- Steatotic liver disease induced by TCPOBOP-activated hepatic constitutive androstane receptor: primary and secondary gene responses with links to disease progression.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Modifications of the GH Axis Reveal Unique Sexually Dimorphic Liver Signatures forJournal of the Endocrine Society · 2024Article
- Article
- Plasma Growth Hormone Pulses Induce Male-biased Pulsatile Chromatin Opening and Epigenetic Regulation in Adult Mouse Liver.bioRxiv : the preprint server for biology · 2023Article
- Assessing the Differential Methylation Analysis Quality for Microarray and NGS Platforms.International journal of molecular sciences · 2023Article
- Genetic variation in the Y chromosome and sex-biased DNA methylation in somatic cells in the mouse.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Article
- Interplay Between GH-regulated, Sex-biased Liver Transcriptome and Hepatic Zonation Revealed by Single-Nucleus RNA Sequencing.Endocrinology · 2022Article
- Growth Hormone and Insulin-Like Growth Factor 1 Regulation of Nonalcoholic Fatty Liver Disease.The Journal of clinical endocrinology and metabolism · 2022 · on this mapReview
- Sex differences in the intergenerational inheritance of metabolic traits.Nature metabolism · 2022Review
- Constitutively Active STAT5b Feminizes Mouse Liver Gene Expression.Endocrinology · 2022Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Growth hormone-activated STAT5b is an essential regulator of sex-differential gene expression in mouse liver; however, its impact on hepatic gene expression and epigenetic responses is poorly understood. Here, we found a substantial, albeit incomplete loss of liver sex bias in hepatocyte-specific STAT5a/STAT5b (collectively, STAT5)-deficient mouse liver. In male liver, many male-biased genes were downregulated in direct association with the loss of STAT5 binding; many female-biased genes, which show low STAT5 binding, were derepressed, indicating an indirect mechanism for repression by STAT5. Extensive changes in CpG methylation were seen in STAT5-deficient liver, where sex differences were abolished at 88% of ∼1,500 sex-differentially methylated regions, largely due to increased DNA methylation upon STAT5 loss. STAT5-dependent CpG hypomethylation was rarely found at proximal promoters of STAT5-dependent genes. Rather, STAT5 primarily regulated the methylation of distal enhancers, where STAT5 deficiency induced widespread hypermethylation at genomic regions enriched for accessible chromatin, enhancer histone marks (histone H3 lysine 4 monomethylation [H3K4me1] and histone H3 lysine 27 acetylation [H3K27ac]), STAT5 binding, and DNA motifs for STAT5 and other transcription factors implicated in liver sex differences. Thus, the sex-dependent binding of STAT5 to liver chromatin is closely linked to the sex-dependent demethylation of distal regulatory elements linked to STAT5-dependent genes important for liver sex bias.
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