ArticleProceedings of the National Academy of Sciences of the United States of America2012
UTX regulates mesoderm differentiation of embryonic stem cells independent of H3K27 demethylase activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
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Who cites it
143 citing papers in PubMed, 218 citations in OpenAlex.
- KDM6A loss enhances oxidative phosphorylation uncovering tissue-level convergent evolution.The EMBO journal · 2026Article
- BAP1 and UTX are dispensable for transcription-driven Polycomb erasure but essential for enhancer establishment.The Journal of biological chemistry · 2026Article
- Enhancer and metabolic rewiring by KMT2C-COMPASS or KMT2D-COMPASS family loss in cancer creates druggable vulnerabilities.Nature reviews. Cancer · 2026Review
- The transcriptional repressor Ssn6 modulates phase separation to regulate fungal gene expression.mBio · 2026Article
- UTY (KDM6C) in Cancer: Epigenetic Regulation, Tumour Suppressor Functions, and Clinical Implications.Epigenomes · 2026Review
- Antagonistic Ubiquitin Switching by USP7 and RNF40 Orchestrates KDM6A Homeostasis to License Coronavirus Susceptibility.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- No Evidence of Impact of Genetic Sex on Hyperthermia-Induced Neural Tube Defects in Chicken Embryos.Birth defects research · 2026Article
- Review
- Histone lysine demethylases in breast cancer: molecular mechanisms, biological functions, and therapeutic intervention.Molecular cancer · 2025Review
- KDM6 Demethylases Contribute to EWSR1::FLI1-Driven Oncogenic Reprogramming in Ewing Sarcoma.Cancer research · 2025Article
- Regulation of Mitochondrial Metabolism byCells · 2025Article
- KDM6B is a conserved activator at the top of the male sex determination pathway.Development (Cambridge, England) · 2025Article
- KDM6A Deficiency Induces Myeloid Bias and Promotes CMML-Like Disease Through JAK/STAT3 Activation by Repressing SOCS3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- UTX (KDM6A) promotes differentiation noncatalytically in somatic self-renewing epithelia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Roles of Kdm6a and Kdm6b in Regulation of Mammalian Neural Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- KDM6A facilitates Xist upregulation at the onset of X inactivation.Biology of sex differences · 2025Article
- Mutation on JmjC domain of UTX impaired its antitumor effects in pancreatic cancer via inhibiting G0S2 expression and activating the Toll-like signaling pathway.Molecular medicine (Cambridge, Mass.) · 2024Article
- Membraneless organelles in health and disease: exploring the molecular basis, physiological roles and pathological implications.Signal transduction and targeted therapy · 2024Review
- Comparing the roles of sex chromosome-encoded protein homologs in gene regulation.Genes & development · 2024Review
83 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
To investigate the role of histone H3K27 demethylase UTX in embryonic stem (ES) cell differentiation, we have generated UTX knockout (KO) and enzyme-dead knock-in male ES cells. Deletion of the X-chromosome-encoded UTX gene in male ES cells markedly decreases expression of the paralogous UTY gene encoded by Y chromosome, but has no effect on global H3K27me3 level, Hox gene expression, or ES cell self-renewal. However, UTX KO cells show severe defects in mesoderm differentiation and induction of Brachyury, a transcription factor essential for mesoderm development. Surprisingly, UTX regulates mesoderm differentiation and Brachyury expression independent of its enzymatic activity. UTY, which lacks detectable demethylase activity, compensates for the loss of UTX in regulating Brachyury expression. UTX and UTY bind directly to Brachyury promoter and are required for Wnt/β-catenin signaling-induced Brachyury expression in ES cells. Interestingly, male UTX KO embryos express normal levels of UTY and survive until birth. In contrast, female UTX KO mice, which lack the UTY gene, show embryonic lethality before embryonic day 11.5. Female UTX KO embryos show severe defects in both Brachyury expression and embryonic development of mesoderm-derived posterior notochord, cardiac, and hematopoietic tissues. These results indicate that UTX controls mesoderm differentiation and Brachyury expression independent of H3K27 demethylase activity, and suggest that UTX and UTY are functionally redundant in ES cell differentiation and early embryonic development.
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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.