ArticleNature neuroscience2015
Brain feminization requires active repression of masculinization via DNA methylation.
Article in Nature neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 209 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
209 citing papers in PubMed, 2 syntheses or guidelines pooled it, 397 citations in OpenAlex.
- Sex effects on DNA methylation affect discovery in epigenome-wide association study of schizophrenia.Molecular psychiatry · 2024Pooled it
- Sex-specific differences in zebrafish brains.Biology of sex differences · 2022Pooled it
- A transient sex-biased transcriptional program shapes early postnatal L2/3 neuron development.Biology of sex differences · 2026Article
- Advancing insights into the neuroendocrine basis of socio-sexual interactions in mammals.Endocrinology · 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
- Sexual dimorphism in cancer: molecular mechanisms and precision oncology perspectives.Biology of sex differences · 2026Review
- Machine learning for individual epigenetic fingerprints as predictors of well-being in young adults.Scientific reports · 2026Article
- Epigenetic regulation of brain development, plasticity, and response to early-life stress.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- A bifunctional optical reporter for tracking estrogen response dynamics in neurons.bioRxiv : the preprint server for biology · 2025Article
- Polycystic ovary syndrome and idiopathic central precocious puberty: two sides of the same coin?Endocrine · 2025Review
- A male-dominant cell group expressing calbindin-D28K and androgen receptor in the mouse preoptic area requires postnatal testicular androgens and histone deacetylation.Journal of neuroendocrinology · 2025Article
- Steroid hormone-mediated epigenetic programming during puberty: uncovering links to depression.Epigenomics · 2025Review
- Sex Bias in Autoimmunity: New Findings and New Opportunities.JID innovations : skin science from molecules to population health · 2025Review
- Gender and sex interactions are intrinsic components of cancer phenotypes.Nature reviews. Cancer · 2025Review
- Maternal high fat and high sugar diet impacts on key DNA methylation enzymes in offspring brain in a sex-specific manner.Journal of neuroendocrinology · 2025Article
- Interplay between prenatal bisphenol exposure, postnatal maternal care, and offspring sex in predicting DNA methylation relevant to anxiety-like behavior in rats.Hormones and behavior · 2025Article
- Modeling the developing nervous system: a neuroscience perspective on the use of new approach methodologies in developmental neurotoxicity testing.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Cumulative risk assessment as the pathway to public health protection for behavioral neurotoxicity.Neurotoxicology · 2025Review
- Insights into pubertal development: a narrative review on the role of epigenetics.Journal of endocrinological investigation · 2025Review
- Review
149 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The developing mammalian brain is destined for a female phenotype unless exposed to gonadal hormones during a perinatal sensitive period. It has been assumed that the undifferentiated brain is masculinized by direct induction of transcription by ligand-activated nuclear steroid receptors. We found that a primary effect of gonadal steroids in the highly sexually dimorphic preoptic area (POA) is to reduce activity of DNA methyltransferase (Dnmt) enzymes, thereby decreasing DNA methylation and releasing masculinizing genes from epigenetic repression. Pharmacological inhibition of Dnmts mimicked gonadal steroids, resulting in masculinized neuronal markers and male sexual behavior in female rats. Conditional knockout of the de novo Dnmt isoform, Dnmt3a, also masculinized sexual behavior in female mice. RNA sequencing revealed gene and isoform variants modulated by methylation that may underlie the divergent reproductive behaviors of males versus females. Our data show that brain feminization is maintained by the active suppression of masculinization via DNA methylation.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.