ArticleCellular and molecular life sciences : CMLS2021
X-linked histone H3K27 demethylase Kdm6a regulates sexually dimorphic differentiation of hypothalamic neurons.
Article in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Firemaster 550 differentially alters gene expression underlying synaptic function in amygdala of prairie voles after gestational or lactational exposure.Neurotoxicology · 2026Article
- Sexual Dimorphism in Spinal Cord Injury: From Molecular Mechanisms to Clinical Translation.Neuromolecular medicine · 2026Review
- Sexual dimorphism in the colonic microbiome and host's transcriptomics profiles of a murine model of multiple sclerosis.Clinical immunology communications · 2026Article
- The inactive X chromosome as a female protector in autism and beyond.Nature genetics · 2026Review
- Sex chromosome-dependent epigenetic regulation underlies sex-specific H4 acetylation at the aromatase promoter in the developing mouse amygdala.Biology of sex differences · 2026Article
- Mechanisms Underlying Treatment-Resistant Depression: Exploring Sex-Based Biological Differences.Journal of neurochemistry · 2025Review
- Influence of Gonadal and Chromosomal Sex on the Brain Transcriptome in a Mouse Species with Natural Sex Reversal.Molecular biology and evolution · 2025Article
- UTX Responds to Nanotopography to Suppress Macrophage Inflammatory Response by Remodeling H3K27me3 Modification.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Strategies for studying sex differences in brain aging.Trends in genetics : TIG · 2025Review
- Survey of gene, lncRNA and transposon transcription patterns in four mouse organs highlights shared and organ-specific sex-biased regulation.Genome biology · 2025Article
- Sex chromosomes/hormones and the tumor microenvironment of non-reproductive cancers.Frontiers in immunology · 2025Review
- Discovery and structural studies of histone demethylases.Frontiers in epigenetics and epigenomics · 2025Review
- Sex-biased gene expression across mammalian organ development and evolution.Science (New York, N.Y.) · 2023Article
- X, but not Y, Chromosomal Complement Contributes to Stroke Sensitivity in Aged Animals.Translational stroke research · 2023Article
- Genetics and Epigenetics of the X and Y Chromosomes in the Sexual Differentiation of the Brain.International journal of molecular sciences · 2022Review
- Cocaine regulation of Nr4a1 chromatin bivalency and mRNA in male and female mice.Scientific reports · 2022Article
- Article
- Epigenetic modifier Kdm6a/Utx controls the specification of hypothalamic neuronal subtypes in a sex-dependent manner.Frontiers in cell and developmental biology · 2022Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Several X-linked genes are involved in neuronal differentiation and may contribute to the generation of sex dimorphisms in the brain. Previous results showed that XX hypothalamic neurons grow faster, have longer axons, and exhibit higher expression of the neuritogenic gene neurogenin 3 (Ngn3) than XY before perinatal masculinization. Here we evaluated the participation of candidate X-linked genes in the development of these sex differences, focusing mainly on Kdm6a, a gene encoding for an H3K27 demethylase with functions controlling gene expression genome-wide. We established hypothalamic neuronal cultures from wild-type or transgenic Four Core Genotypes mice, a model that allows evaluating the effect of sex chromosomes independently of gonadal type. X-linked genes Kdm6a, Eif2s3x and Ddx3x showed higher expression in XX compared to XY neurons, regardless of gonadal sex. Moreover, Kdm6a expression pattern with higher mRNA levels in XX than XY did not change with age at E14, P0, and P60 in hypothalamus or under 17β-estradiol treatment in culture. Kdm6a pharmacological blockade by GSK-J4 reduced axonal length only in female neurons and decreased the expression of neuritogenic genes Neurod1, Neurod2 and Cdk5r1 in both sexes equally, while a sex-specific effect was observed in Ngn3. Finally, Kdm6a downregulation using siRNA reduced axonal length and Ngn3 expression only in female neurons, abolishing the sex differences observed in control conditions. Altogether, these results point to Kdm6a as a key mediator of the higher axogenesis and Ngn3 expression observed in XX neurons before the critical period of brain masculinization.
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